NM_005581.5:c.230G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005581.5(BCAM):c.230G>A(p.Arg77His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,602,760 control chromosomes in the GnomAD database, including 716 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 66 hom., cov: 32)

Exomes 𝑓: 0.028 ( 650 hom. )

Consequence

BCAM
NM_005581.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.84

Publications

35 publications found

Variant links:

Genes affected

BCAM (HGNC:6722): (basal cell adhesion molecule (Lutheran blood group)) This gene encodes Lutheran blood group glycoprotein, a member of the immunoglobulin superfamily and a receptor for the extracellular matrix protein, laminin. The protein contains five extracellular immunoglobulin domains, a single transmembrane domain, and a short C-terminal cytoplasmic tail. This protein may play a role in epithelial cell cancer and in vaso-occlusion of red blood cells in sickle cell disease. Polymorphisms in this gene define some of the antigens in the Lutheran system and also the Auberger system. Inactivating variants of this gene result in the recessive Lutheran null phenotype, Lu(a-b-), of the Lutheran blood group. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

BCAM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037329793).

BP6

Variant 19-44812188-G-A is Benign according to our data. Variant chr19-44812188-G-A is described in CliVar as Benign. Clinvar id is 438.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-44812188-G-A is described in CliVar as Benign. Clinvar id is 438.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-44812188-G-A is described in CliVar as Benign. Clinvar id is 438.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-44812188-G-A is described in CliVar as Benign. Clinvar id is 438.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-44812188-G-A is described in CliVar as Benign. Clinvar id is 438.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-44812188-G-A is described in CliVar as Benign. Clinvar id is 438.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-44812188-G-A is described in CliVar as Benign. Clinvar id is 438.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-44812188-G-A is described in CliVar as Benign. Clinvar id is 438.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-44812188-G-A is described in CliVar as Benign. Clinvar id is 438.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-44812188-G-A is described in CliVar as Benign. Clinvar id is 438.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0265 (4040/152312) while in subpopulation NFE AF = 0.0314 (2139/68020). AF 95% confidence interval is 0.0303. There are 66 homozygotes in GnomAd4. There are 1901 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 66 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAM	NM_005581.5 link	c.230G>A	p.Arg77His	missense_variant	Exon 3 of 15	ENST00000270233.12	NP_005572.2	P50895
BCAM	NM_001013257.2 link	c.230G>A	p.Arg77His	missense_variant	Exon 3 of 14		NP_001013275.1	P50895A0A087WXM8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAM	ENST00000270233.12 link	c.230G>A	p.Arg77His	missense_variant	Exon 3 of 15	1	NM_005581.5	ENSP00000270233.5		P50895

Frequencies

GnomAD3 genomes

AF:

0.0265

AC:

4027

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0243

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0314

Gnomad OTH

AF:

0.0353

GnomAD2 exomes

AF:

0.0214

AC:

4896

AN:

229008

AF XY:

0.0207

show subpopulations

Gnomad AFR exome

AF:

0.0285

Gnomad AMR exome

AF:

0.0149

Gnomad ASJ exome

AF:

0.0251

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0120

Gnomad NFE exome

AF:

0.0327

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.0282

AC:

40835

AN:

1450448

Hom.:

650

Cov.:

AF XY:

0.0272

AC XY:

19642

AN XY:

722174

show subpopulations

African (AFR)

AF:

0.0286

AC:

936

AN:

32700

American (AMR)

AF:

0.0164

AC:

668

AN:

40680

Ashkenazi Jewish (ASJ)

AF:

0.0261

AC:

670

AN:

25664

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39648

South Asian (SAS)

AF:

0.00183

AC:

156

AN:

85462

European-Finnish (FIN)

AF:

0.0133

AC:

684

AN:

51342

Middle Eastern (MID)

AF:

0.0146

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.0326

AC:

36134

AN:

1109428

Other (OTH)

AF:

0.0251

AC:

1503

AN:

59828

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2502

5004

7505

10007

12509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1344

2688

4032

5376

6720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0265

AC:

4040

AN:

152312

Hom.:

Cov.:

AF XY:

0.0255

AC XY:

1901

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0294

AC:

1224

AN:

41568

American (AMR)

AF:

0.0243

AC:

372

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0282

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.00249

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0103

AC:

110

AN:

10628

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0314

AC:

2139

AN:

68020

Other (OTH)

AF:

0.0350

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

212

424

635

847

1059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0310

Hom.:

223

Bravo

AF:

0.0285

TwinsUK

AF:

0.0359

AC:

133

ALSPAC

AF:

0.0389

AC:

150

ESP6500AA

AF:

0.0284

AC:

124

ESP6500EA

AF:

0.0324

AC:

277

ExAC

AF:

0.0219

AC:

2653

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

LUTHERAN BLOOD GROUP POLYMORPHISM Lu(a)/Lu(b)

Benign:1

Dec 30, 2010

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.8

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.64

T;T

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.

PhyloP100

-1.8

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.035

Sift

Uncertain

0.017

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.068

B;.

Vest4

0.089

MPC

0.26

ClinPred

0.015

GERP RS

-0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.22

gMVP

0.63

Mutation Taster

=88/12

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over