19-44813447-T-A

Position:

chr19-44813447-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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 criteria provided, single submitter B:1

Conservation

PhyloP100: 0.502

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 -14 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 id is 3060945.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome 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 gnomad4_exome. There are 7502 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCAM	NM_005581.5 linkuse as main transcript	c.611T>A	p.Met204Lys	missense_variant	6/15	ENST00000270233.12
BCAM	NM_001013257.2 linkuse as main transcript	c.611T>A	p.Met204Lys	missense_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCAM	ENST00000270233.12 linkuse as main transcript	c.611T>A	p.Met204Lys	missense_variant	6/15	1	NM_005581.5	P1

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

GnomAD3 exomes

AF:

0.00949

AC:

2316

AN:

244166

Hom.:

AF XY:

0.00947

AC XY:

1259

AN XY:

132956

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 SAS exome

AF:

0.00305

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

Gnomad4 AFR exome

AF:

0.00132

Gnomad4 AMR exome

AF:

0.00694

Gnomad4 ASJ exome

AF:

0.0150

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00310

Gnomad4 FIN exome

AF:

0.0109

Gnomad4 NFE exome

AF:

0.0114

Gnomad4 OTH exome

AF:

0.00978

GnomAD4 genome

AF:

0.00937

AC:

1427

AN:

152302

Hom.:

Cov.:

AF XY:

0.00935

AC XY:

696

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.0181

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00932

Gnomad4 NFE

AF:

0.0143

Gnomad4 OTH

AF:

0.0118

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

BCAM-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as likely 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

0.15

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.26

T;T;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.48

T;T;T

MetaRNN

Benign

0.0060

T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.2

M;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.2

N;.;.

REVEL

Benign

0.071

Sift

Uncertain

0.016

D;.;.

Sift4G

Uncertain

0.027

D;D;D

Polyphen

0.42

B;.;.

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

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

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