19-44813550-C-T

Variant names:

• chr19-44813550-C-T
• rs3810140
• NM_005581.5:c.714C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_005581.5(BCAM):​c.714C>T​(p.Ala238Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 1,612,542 control chromosomes in the GnomAD database, including 4,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.073 (458 hom., cov: 32)
  • Exomes 𝑓: 0.067 (4230 hom.)
• Consequence: BCAM NM_005581.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.37

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 19-44813550-C-T is Benign according to our data. Variant chr19-44813550-C-T is described in ClinVar as [Benign]. Clinvar id is 3056244.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-3.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAM	NM_005581.5	c.714C>T	p.Ala238Ala	synonymous_variant	Exon 6 of 15	ENST00000270233.12	NP_005572.2
BCAM	NM_001013257.2	c.714C>T	p.Ala238Ala	synonymous_variant	Exon 6 of 14		NP_001013275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAM	ENST00000270233.12	c.714C>T	p.Ala238Ala	synonymous_variant	Exon 6 of 15	1	NM_005581.5	ENSP00000270233.5

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11125 AN: 152124 Hom.: 457 Cov.: 32

Gnomad AFR AF: 0.0657

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.0308

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0655

Gnomad OTH AF: 0.0757

GnomAD2 exomes AF: 0.0842 AC: 20770 AN: 246704 AF XY: 0.0892

Gnomad AFR exome AF: 0.0677

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.0450

Gnomad EAS exome AF: 0.0337

Gnomad FIN exome AF: 0.0723

Gnomad NFE exome AF: 0.0651

Gnomad OTH exome AF: 0.0771

GnomAD4 exome AF: 0.0672 AC: 98167 AN: 1460300 Hom.: 4230 Cov.: 33 AF XY: 0.0710 AC XY: 51582 AN XY: 726562

Gnomad4 AFR exome AF: 0.0643 AC: 2152 AN: 33474

Gnomad4 AMR exome AF: 0.114 AC: 5108 AN: 44704

Gnomad4 ASJ exome AF: 0.0418 AC: 1091 AN: 26114

Gnomad4 EAS exome AF: 0.0319 AC: 1268 AN: 39696

Gnomad4 SAS exome AF: 0.178 AC: 15339 AN: 86248

Gnomad4 FIN exome AF: 0.0725 AC: 3771 AN: 52038

Gnomad4 NFE exome AF: 0.0583 AC: 64861 AN: 1111882

Gnomad4 Remaining exome AF: 0.0693 AC: 4182 AN: 60376

GnomAD4 genome AF: 0.0731 AC: 11136 AN: 152242 Hom.: 458 Cov.: 32 AF XY: 0.0767 AC XY: 5708 AN XY: 74442

Gnomad4 AFR AF: 0.0658 AC: 0.0657521 AN: 0.0657521

Gnomad4 AMR AF: 0.115 AC: 0.114796 AN: 0.114796

Gnomad4 ASJ AF: 0.0479 AC: 0.0479215 AN: 0.0479215

Gnomad4 EAS AF: 0.0309 AC: 0.0308761 AN: 0.0308761

Gnomad4 SAS AF: 0.178 AC: 0.178349 AN: 0.178349

Gnomad4 FIN AF: 0.0754 AC: 0.0753721 AN: 0.0753721

Gnomad4 NFE AF: 0.0655 AC: 0.0654776 AN: 0.0654776

Gnomad4 OTH AF: 0.0749 AC: 0.0748815 AN: 0.0748815

Alfa AF: 0.0376 Hom.: 86

Bravo AF: 0.0714

Asia WGS AF: 0.116 AC: 402 AN: 3478

EpiCase AF: 0.0628

EpiControl AF: 0.0648

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

BCAM-related disorder Benign:1

Jan 02, 2020

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
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.25
DANN	Benign	0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3810140; hg19: chr19-45316807; COSMIC: COSV54302950; COSMIC: COSV54302950;