rs8101274

Positions:

• chr19-44813933-G-A
• chr19-44813933-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005581.5(BCAM):​c.785-219G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0388 in 152,134 control chromosomes in the GnomAD database, including 303 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 0.039 (303 hom., cov: 32)
• Consequence: BCAM NM_005581.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.895

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCAM	NM_005581.5	c.785-219G>A		intron_variant		ENST00000270233.12	NP_005572.2
BCAM	NM_001013257.2	c.785-219G>A		intron_variant			NP_001013275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCAM	ENST00000270233.12	c.785-219G>A		intron_variant		1	NM_005581.5	ENSP00000270233	P1
BCAM	ENST00000591520.6	c.722-219G>A		intron_variant		3		ENSP00000467100
BCAM	ENST00000611077.5	c.785-219G>A		intron_variant		5		ENSP00000481153
BCAM	ENST00000590196.1	c.183+313G>A		intron_variant, NMD_transcript_variant		5		ENSP00000468189

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5892 AN: 152016 Hom.: 303 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0554

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00250

Gnomad OTH AF: 0.0407

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

GnomAD4 genome AF: 0.0388 AC: 5896 AN: 152134 Hom.: 303 Cov.: 32 AF XY: 0.0389 AC XY: 2890 AN XY: 74354

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0217

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.0559

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.00250

Gnomad4 OTH AF: 0.0432

Alfa AF: 0.0130 Hom.: 23

Bravo AF: 0.0421

Asia WGS AF: 0.105 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.46

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: rs8101274; hg19: chr19-45317190;