chr19-44810458-T-C

Variant names:

• chr19-44810458-T-C
• rs2927477
• NM_005581.5:c.83-767T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005581.5(BCAM):​c.83-767T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 148,356 control chromosomes in the GnomAD database, including 3,853 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3853 hom., cov: 31)
• Consequence: BCAM NM_005581.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAM	NM_005581.5	c.83-767T>C		intron_variant	Intron 1 of 14	ENST00000270233.12	NP_005572.2
BCAM	NM_001013257.2	c.83-767T>C		intron_variant	Intron 1 of 13		NP_001013275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCAM	ENST00000270233.12	c.83-767T>C		intron_variant	Intron 1 of 14	1	NM_005581.5	ENSP00000270233.5

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30178 AN: 148216 Hom.: 3831 Cov.: 31

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.204 AC: 30255 AN: 148356 Hom.: 3853 Cov.: 31 AF XY: 0.206 AC XY: 14875 AN XY: 72340

African (AFR) AF: 0.364 AC: 14833 AN: 40726

American (AMR) AF: 0.189 AC: 2818 AN: 14878

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 425 AN: 3440

East Asian (EAS) AF: 0.160 AC: 762 AN: 4752

South Asian (SAS) AF: 0.297 AC: 1353 AN: 4550

European-Finnish (FIN) AF: 0.103 AC: 1008 AN: 9790

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.127 AC: 8481 AN: 66966

Other (OTH) AF: 0.201 AC: 419 AN: 2080

Alfa AF: 0.174 Hom.: 368

Bravo AF: 0.209

Asia WGS AF: 0.255 AC: 885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		1.0
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: rs2927477; hg19: chr19-45313715;