19-44812545-G-C

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005581.5(BCAM):c.501G>C(p.Gln167His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

BCAM
NM_005581.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.520

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055620015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCAM	NM_005581.5 link	c.501G>C	p.Gln167His	missense_variant	Exon 4 of 15	ENST00000270233.12	NP_005572.2	P50895
BCAM	NM_001013257.2 link	c.501G>C	p.Gln167His	missense_variant	Exon 4 of 14		NP_001013275.1	P50895A0A087WXM8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BCAM	ENST00000270233.12 link	c.501G>C	p.Gln167His	missense_variant	Exon 4 of 15	1	NM_005581.5	ENSP00000270233.5	P50895
BCAM	ENST00000611077.5 link	c.501G>C	p.Gln167His	missense_variant	Exon 4 of 14	5		ENSP00000481153.1	A0A087WXM8
BCAM	ENST00000591520.6 link	c.438G>C	p.Gln146His	missense_variant	Exon 4 of 7	3		ENSP00000467100.2	K7ENU8
BCAM	ENST00000588603.1 link	n.496G>C		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251140

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000123

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.501G>C (p.Q167H) alteration is located in exon 4 (coding exon 4) of the BCAM gene. This alteration results from a G to C substitution at nucleotide position 501, causing the glutamine (Q) at amino acid position 167 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.25

T;T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.68

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.62

T;T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.3

L;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.5

N;.;.

REVEL

Benign

0.19

Sift

Benign

0.099

T;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.0050

B;.;.

Vest4

0.19

MutPred

0.44

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;

MVP

0.43

MPC

0.25

ClinPred

0.018

GERP RS

-3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.29

gMVP

0.64

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over