Variant 19-44812188-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005581.5(BCAM):c.230G>C(p.Arg77Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R77H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

BCAM
NM_005581.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.84

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:

BCAM (HGNC:):

BCAM links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14366472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCAM	NM_005581.5 linkuse as main transcript	c.230G>C	p.Arg77Pro	missense_variant	3/15	ENST00000270233.12	NP_005572.2	P50895
BCAM	NM_001013257.2 linkuse as main transcript	c.230G>C	p.Arg77Pro	missense_variant	3/14		NP_001013275.1	P50895A0A087WXM8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BCAM	ENST00000270233.12 linkuse as main transcript	c.230G>C	p.Arg77Pro	missense_variant	3/15	1	NM_005581.5	ENSP00000270233.5	P50895
BCAM	ENST00000611077.5 linkuse as main transcript	c.230G>C	p.Arg77Pro	missense_variant	3/14	5		ENSP00000481153.1	A0A087WXM8
BCAM	ENST00000591520.6 linkuse as main transcript	c.205-38G>C		intron_variant		3		ENSP00000467100.2	K7ENU8
BCAM	ENST00000588603.1 linkuse as main transcript	n.225G>C		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000437

AC:

AN:

229008

Hom.:

AF XY:

0.00000792

AC XY:

AN XY:

126314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450466

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.44

CADD

Benign

3.2

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

M;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.10

Sift

Uncertain

0.016

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.018

B;.

Vest4

0.40

MutPred

0.56

Gain of glycosylation at R77 (P = 0.0146);Gain of glycosylation at R77 (P = 0.0146);

MVP

0.055

MPC

0.32

ClinPred

0.071

GERP RS

-0.14

Varity_R

0.93

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over