chr19-44809161-G-A

Variant names:

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

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>A​(p.Ala13Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,322,076 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. 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. A13S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: BCAM NM_005581.5 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.230189).

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>A	p.Ala13Thr	missense	Exon 1 of 15	NP_005572.2
	BCAM	NM_001013257.2		c.37G>A	p.Ala13Thr	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>A	p.Ala13Thr	missense	Exon 1 of 15	ENSP00000270233.5	P50895
	BCAM	ENST00000940906.1		c.37G>A	p.Ala13Thr	missense	Exon 1 of 15	ENSP00000610965.1
	BCAM	ENST00000852016.1		c.37G>A	p.Ala13Thr	missense	Exon 1 of 15	ENSP00000522075.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000151 AC: 2 AN: 1322076 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 651530

African (AFR) AF: 0.00 AC: 0 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: 0.0000137 AC: 1 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: 9.54e-7 AC: 1 AN: 1048068

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.2
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.097
Sift	Benign	0.16	T
Sift4G	Benign	0.093	T
Polyphen		0.76	P
Vest4		0.22
MutPred		0.36		Loss of helix (P = 0.0041)
MVP		0.53
MPC		0.29
ClinPred		0.30	T
GERP RS		2.5
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.047
gMVP		0.32
Mutation Taster		=92/8	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;