rs935885

Variant names:

• chr15-44718817-C-A
• rs935885
• ENST00000561424.5:n.*172C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-44718817-C-A
• chr15-44718817-C-G
• chr15-44718817-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000561424.5(B2M):​n.*172C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 152,280 control chromosomes in the GnomAD database, including 67,628 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.94 (67627 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: B2M ENST00000561424.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 4 publications found

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]

B2M Gene-Disease associations (from GenCC):

• hypoproteinemia, hypercatabolic

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• variant ABeta2M amyloidosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• MHC class I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• familial visceral amyloidosis

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B2M	ENST00000561424.5	n.*172C>A		non_coding_transcript_exon_variant	Exon 5 of 5	3		ENSP00000453191.1
B2M	ENST00000561424.5	n.*172C>A		3_prime_UTR_variant	Exon 5 of 5	3		ENSP00000453191.1

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143271 AN: 152160 Hom.: 67581 Cov.: 31

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.950

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.957

Gnomad OTH AF: 0.936

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.942 AC: 143376 AN: 152278 Hom.: 67627 Cov.: 31 AF XY: 0.939 AC XY: 69912 AN XY: 74442

African (AFR) AF: 0.954 AC: 39625 AN: 41556

American (AMR) AF: 0.884 AC: 13508 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 3299 AN: 3472

East Asian (EAS) AF: 0.838 AC: 4340 AN: 5182

South Asian (SAS) AF: 0.861 AC: 4153 AN: 4826

European-Finnish (FIN) AF: 0.964 AC: 10230 AN: 10616

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.957 AC: 65087 AN: 68032

Other (OTH) AF: 0.936 AC: 1978 AN: 2114

Alfa AF: 0.950 Hom.: 23800

Bravo AF: 0.935

Asia WGS AF: 0.860 AC: 2994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.37
DANN	Benign	0.41
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs935885; hg19: chr15-45011015;