19-44809161-G-T

Variant names:

• chr19-44809161-G-T
• rs1968383919
• NM_005581.5:c.37G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005581.5(BCAM):​c.37G>T​(p.Ala13Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000136 in 1,474,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: BCAM NM_005581.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18323615).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005581.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAM	NM_005581.5	MANE Select	c.37G>T	p.Ala13Ser	missense	Exon 1 of 15	NP_005572.2
	BCAM	NM_001013257.2		c.37G>T	p.Ala13Ser	missense	Exon 1 of 14	NP_001013275.1	A0A087WXM8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCAM	ENST00000270233.12	TSL:1 MANE Select	c.37G>T	p.Ala13Ser	missense	Exon 1 of 15	ENSP00000270233.5	P50895
	BCAM	ENST00000940906.1		c.37G>T	p.Ala13Ser	missense	Exon 1 of 15	ENSP00000610965.1
	BCAM	ENST00000852016.1		c.37G>T	p.Ala13Ser	missense	Exon 1 of 15	ENSP00000522075.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151956 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.56e-7 AC: 1 AN: 1322078 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 651532

African (AFR) AF: 0.0000370 AC: 1 AN: 26994

American (AMR) AF: 0.00 AC: 0 AN: 27524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23408

East Asian (EAS) AF: 0.00 AC: 0 AN: 28434

South Asian (SAS) AF: 0.00 AC: 0 AN: 72938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4202

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1048070

Other (OTH) AF: 0.00 AC: 0 AN: 54662

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151956 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74214

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67924

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.54	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.2
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.061
Sift	Benign	0.46	T
Sift4G	Benign	0.21	T
Polyphen		0.61	P
Vest4		0.28
MutPred		0.34		Loss of helix (P = 0.0041)
MVP		0.50
MPC		0.22
ClinPred		0.18	T
GERP RS		2.5
PromoterAI		-0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.060
gMVP		0.30
Mutation Taster		=96/4	polymorphism

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: rs1968383919; hg19: chr19-45312418;