rs1440025860

Variant names:

• chr15-44711578-C-A
• NM_004048.4:c.32C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-44711578-C-A
• chr15-44711578-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_004048.4(B2M):​c.32C>A​(p.Ala11Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A11P) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: B2M NM_004048.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592

Genes affected

B2M (HGNC:914): (beta-2-microglobulin) This gene encodes a serum protein found in association with the major histocompatibility complex (MHC) class I heavy chain on the surface of nearly all nucleated cells. The protein has a predominantly beta-pleated sheet structure that can form amyloid fibrils in some pathological conditions. The encoded antimicrobial protein displays antibacterial activity in amniotic fluid. A mutation in this gene has been shown to result in hypercatabolic hypoproteinemia.[provided by RefSeq, Aug 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr15-44711577-G-C is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.22679928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B2M	NM_004048.4	c.32C>A	p.Ala11Glu	missense_variant	Exon 1 of 4	ENST00000648006.3	NP_004039.1
B2M	XM_005254549.4	c.32C>A	p.Ala11Glu	missense_variant	Exon 1 of 2		XP_005254606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B2M	ENST00000648006.3	c.32C>A	p.Ala11Glu	missense_variant	Exon 1 of 4		NM_004048.4	ENSP00000497910.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.2
DANN	Benign	0.66
DEOGEN2	Benign	0.044	T;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.16	N
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	.;L;L;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N;N;N;.
REVEL	Benign	0.18
Sift	Benign	0.074	T;T;T;.
Sift4G	Benign	0.082	T;T;T;.
Polyphen		0.87	P;P;P;P
Vest4		0.30
MutPred		0.66		Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);
MVP		0.34
MPC		0.92
ClinPred		0.90	D
GERP RS		-8.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-45003776;