rs1135062

chr19-44819487-A-G

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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:3

Conservation

PhyloP100: -1.90

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
BCAM	NM_005581.5 linkuse as main transcript	c.1615A>G	p.Thr539Ala	missense_variant	12/15	ENST00000270233.12
BCAM	NM_001013257.2 linkuse as main transcript	c.1615A>G	p.Thr539Ala	missense_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
BCAM	ENST00000270233.12 linkuse as main transcript	c.1615A>G	p.Thr539Ala	missense_variant	12/15	1	NM_005581.5	P1
BCAM	ENST00000611077.5 linkuse as main transcript	c.1615A>G	p.Thr539Ala	missense_variant	12/14	5
BCAM	ENST00000588714.1 linkuse as main transcript	n.241A>G		non_coding_transcript_exon_variant	1/2	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

GnomAD3 exomes

AF:

0.273

AC:

68448

AN:

251102

Hom.:

10132

AF XY:

0.273

AC XY:

37093

AN XY:

135744

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 SAS exome

AF:

0.229

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

Gnomad4 AFR exome

AF:

0.426

Gnomad4 AMR exome

AF:

0.218

Gnomad4 ASJ exome

AF:

0.307

Gnomad4 EAS exome

AF:

0.0770

Gnomad4 SAS exome

AF:

0.230

Gnomad4 FIN exome

AF:

0.299

Gnomad4 NFE exome

AF:

0.294

Gnomad4 OTH exome

AF:

0.292

GnomAD4 genome

AF:

0.321

AC:

48815

AN:

152028

Hom.:

8183

Cov.:

AF XY:

0.319

AC XY:

23662

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.412

Gnomad4 AMR

AF:

0.289

Gnomad4 ASJ

AF:

0.298

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.221

Gnomad4 FIN

AF:

0.303

Gnomad4 NFE

AF:

0.299

Gnomad4 OTH

AF:

0.332

Alfa

AF:

0.306

Hom.:

12574

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Mar 01, 2007

- -

BLOOD GROUP--LUTHERAN SYSTEM;C1292230:LuLu phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 11, 2021

- -

BCAM-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

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;.

MutationTaster

Benign

1.0

P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over