chr19-44813447-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_005581.5(BCAM):c.611T>A(p.Met204Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,610,918 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0094 ( 12 hom., cov: 32)

Exomes 𝑓: 0.010 ( 130 hom. )

Consequence

BCAM
NM_005581.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.502

Publications

16 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005984366).

BP6

Variant 19-44813447-T-A is Benign according to our data. Variant chr19-44813447-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3060945.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0103 (14968/1458616) while in subpopulation MID AF = 0.021 (121/5764). AF 95% confidence interval is 0.018. There are 130 homozygotes in GnomAdExome4. There are 7502 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 BG gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005581.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAM	NM_005581.5	MANE Select	c.611T>A	p.Met204Lys	missense	Exon 6 of 15	NP_005572.2
	BCAM	NM_001013257.2		c.611T>A	p.Met204Lys	missense	Exon 6 of 14	NP_001013275.1	A0A087WXM8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCAM	ENST00000270233.12	TSL:1 MANE Select	c.611T>A	p.Met204Lys	missense	Exon 6 of 15	ENSP00000270233.5	P50895
BCAM	ENST00000940906.1		c.611T>A	p.Met204Lys	missense	Exon 6 of 15	ENSP00000610965.1
BCAM	ENST00000852016.1		c.563T>A	p.Met188Lys	missense	Exon 6 of 15	ENSP00000522075.1

Frequencies

GnomAD3 genomes

AF:

0.00938

AC:

1428

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.0181

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00932

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0144

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.00949

AC:

2316

AN:

244166

AF XY:

0.00947

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00665

Gnomad ASJ exome

AF:

0.0143

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00981

Gnomad NFE exome

AF:

0.0143

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.0103

AC:

14968

AN:

1458616

Hom.:

130

Cov.:

AF XY:

0.0103

AC XY:

7502

AN XY:

725620

show subpopulations

African (AFR)

AF:

0.00132

AC:

AN:

33458

American (AMR)

AF:

0.00694

AC:

310

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

392

AN:

26090

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39666

South Asian (SAS)

AF:

0.00310

AC:

267

AN:

86194

European-Finnish (FIN)

AF:

0.0109

AC:

558

AN:

51202

Middle Eastern (MID)

AF:

0.0210

AC:

121

AN:

5764

European-Non Finnish (NFE)

AF:

0.0114

AC:

12683

AN:

1111256

Other (OTH)

AF:

0.00978

AC:

590

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

978

1956

2934

3912

4890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.00937

AC:

1427

AN:

152302

Hom.:

Cov.:

AF XY:

0.00935

AC XY:

696

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00171

AC:

AN:

41564

American (AMR)

AF:

0.0116

AC:

177

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0181

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00290

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00932

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0143

AC:

975

AN:

68020

Other (OTH)

AF:

0.0118

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

159

239

318

398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0147

Hom.:

Bravo

AF:

0.00825

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0123

AC:

105

ExAC

AF:

0.00932

AC:

1130

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0141

EpiControl

AF:

0.0111

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

BCAM-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.26

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.2

PhyloP100

0.50

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.2

REVEL

Benign

0.071

Sift

Uncertain

0.016

Sift4G

Uncertain

0.027

Polyphen

0.42

Vest4

0.65

MVP

0.56

MPC

0.71

ClinPred

0.020

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.51

gMVP

0.87

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over