rs1135062

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005581.5(BCAM):c.1615A>G(p.Thr539Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,613,632 control chromosomes in the GnomAD database, including 69,947 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T539T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.32 ( 8183 hom., cov: 32)

Exomes 𝑓: 0.29 ( 61764 hom. )

Consequence

BCAM
NM_005581.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.90

Publications

43 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.84917E-4).

BP6

Variant 19-44819487-A-G is Benign according to our data. Variant chr19-44819487-A-G is described in ClinVar as Benign. ClinVar VariationId is 439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAM	NM_005581.5 link	c.1615A>G	p.Thr539Ala	missense_variant	Exon 12 of 15	ENST00000270233.12	NP_005572.2
BCAM	NM_001013257.2 link	c.1615A>G	p.Thr539Ala	missense_variant	Exon 12 of 14		NP_001013275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
BCAM	ENST00000270233.12 link	c.1615A>G	p.Thr539Ala	missense_variant	Exon 12 of 15	1	NM_005581.5	ENSP00000270233.5
BCAM	ENST00000611077.5 link	c.1615A>G	p.Thr539Ala	missense_variant	Exon 12 of 14	5		ENSP00000481153.1
BCAM	ENST00000588714.1 link	n.241A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2
BCAM	ENST00000589558.1 link	n.*243A>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48772

AN:

151910

Hom.:

8175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.413

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.333

GnomAD2 exomes

AF:

0.273

AC:

68448

AN:

251102

AF XY:

0.273

show subpopulations

Gnomad AFR exome

AF:

0.418

Gnomad AMR exome

AF:

0.210

Gnomad ASJ exome

AF:

0.309

Gnomad EAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.300

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.286

AC:

417311

AN:

1461604

Hom.:

61764

Cov.:

AF XY:

0.284

AC XY:

206435

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.426

AC:

14250

AN:

33480

American (AMR)

AF:

0.218

AC:

9730

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

8033

AN:

26130

East Asian (EAS)

AF:

0.0770

AC:

3058

AN:

39700

South Asian (SAS)

AF:

0.230

AC:

19829

AN:

86258

European-Finnish (FIN)

AF:

0.299

AC:

15956

AN:

53324

Middle Eastern (MID)

AF:

0.324

AC:

1870

AN:

5764

European-Non Finnish (NFE)

AF:

0.294

AC:

326954

AN:

1111860

Other (OTH)

AF:

0.292

AC:

17631

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

20837

41673

62510

83346

104183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10704

21408

32112

42816

53520

<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:

0.321

AC:

48815

AN:

152028

Hom.:

8183

Cov.:

AF XY:

0.319

AC XY:

23662

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.412

AC:

17095

AN:

41454

American (AMR)

AF:

0.289

AC:

4412

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

1034

AN:

3472

East Asian (EAS)

AF:

0.101

AC:

524

AN:

5164

South Asian (SAS)

AF:

0.221

AC:

1064

AN:

4814

European-Finnish (FIN)

AF:

0.303

AC:

3206

AN:

10594

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.299

AC:

20345

AN:

67946

Other (OTH)

AF:

0.332

AC:

699

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1738

3476

5214

6952

8690

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.309

Hom.:

19961

Bravo

AF:

0.323

TwinsUK

AF:

0.294

AC:

1091

ALSPAC

AF:

0.283

AC:

1092

ESP6500AA

AF:

0.409

AC:

1803

ESP6500EA

AF:

0.301

AC:

2588

ExAC

AF:

0.275

AC:

33405

Asia WGS

AF:

0.190

AC:

661

AN:

3478

EpiCase

AF:

0.312

EpiControl

AF:

0.308

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

AUBERGER BLOOD GROUP POLYMORPHISM Au(a)/Au(b)

Benign:1

Mar 01, 2007

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

BLOOD GROUP--LUTHERAN SYSTEM;C1292230:LuLu phenotype

Benign:1

Oct 11, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

BCAM-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.74

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.069

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.30

T;T

MetaRNN

Benign

0.00068

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

L;.

PhyloP100

-1.9

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.20

N;.

REVEL

Benign

0.062

Sift

Benign

0.66

T;.

Sift4G

Benign

0.29

T;T

Polyphen

0.0

B;.

Vest4

0.014

MPC

0.20

ClinPred

0.0055

GERP RS

-8.3

Varity_R

0.017

gMVP

0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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