19-44813547-C-T

Variant names:

• chr19-44813547-C-T
• rs3810141
• NM_005581.5:c.711C>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.711C>T​(p.Cys237Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 1,612,474 control chromosomes in the GnomAD database, including 4,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.081 (543 hom., cov: 32)
  • Exomes 𝑓: 0.068 (4334 hom.)
• Consequence: BCAM NM_005581.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.375
• Publications: 13 publications found

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=-0.83).
• BP6: Variant 19-44813547-C-T is Benign according to our data. Variant chr19-44813547-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056456.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.375 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.711C>T	p.Cys237Cys	synonymous_variant	Exon 6 of 15	ENST00000270233.12	NP_005572.2
BCAM	NM_001013257.2	c.711C>T	p.Cys237Cys	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.711C>T	p.Cys237Cys	synonymous_variant	Exon 6 of 15	1	NM_005581.5	ENSP00000270233.5

Frequencies

GnomAD3 genomes AF: 0.0810 AC: 12329 AN: 152126 Hom.: 542 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.0308

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0753

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0656

Gnomad OTH AF: 0.0828

GnomAD2 exomes AF: 0.0862 AC: 21250 AN: 246500 AF XY: 0.0906

Gnomad AFR exome AF: 0.0944

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.0451

Gnomad EAS exome AF: 0.0336

Gnomad FIN exome AF: 0.0728

Gnomad NFE exome AF: 0.0653

Gnomad OTH exome AF: 0.0782

GnomAD4 exome AF: 0.0681 AC: 99425 AN: 1460230 Hom.: 4334 Cov.: 33 AF XY: 0.0717 AC XY: 52074 AN XY: 726542

African (AFR) AF: 0.0946 AC: 3166 AN: 33478

American (AMR) AF: 0.116 AC: 5170 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 1091 AN: 26110

East Asian (EAS) AF: 0.0320 AC: 1269 AN: 39696

South Asian (SAS) AF: 0.178 AC: 15343 AN: 86250

European-Finnish (FIN) AF: 0.0725 AC: 3769 AN: 51960

Middle Eastern (MID) AF: 0.0690 AC: 398 AN: 5768

European-Non Finnish (NFE) AF: 0.0584 AC: 64941 AN: 1111884

Other (OTH) AF: 0.0709 AC: 4278 AN: 60374

GnomAD4 genome AF: 0.0810 AC: 12338 AN: 152244 Hom.: 543 Cov.: 32 AF XY: 0.0843 AC XY: 6279 AN XY: 74440

African (AFR) AF: 0.0928 AC: 3857 AN: 41556

American (AMR) AF: 0.118 AC: 1809 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 166 AN: 3466

East Asian (EAS) AF: 0.0309 AC: 160 AN: 5180

South Asian (SAS) AF: 0.178 AC: 860 AN: 4824

European-Finnish (FIN) AF: 0.0753 AC: 800 AN: 10618

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0656 AC: 4461 AN: 67996

Other (OTH) AF: 0.0819 AC: 173 AN: 2112

Alfa AF: 0.0652 Hom.: 301

Bravo AF: 0.0800

Asia WGS AF: 0.117 AC: 407 AN: 3478

EpiCase AF: 0.0629

EpiControl AF: 0.0650

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

BCAM-related disorder Benign:1

Dec 23, 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
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.85
PhyloP100		-0.38
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

Other links and lift over

dbSNP: rs3810141; hg19: chr19-45316804; COSMIC: COSV54304151; COSMIC: COSV54304151;