NM_004048.4:c.*232A>G

Variant names:

• chr15-44717824-A-G
• rs4780
• NM_004048.4:c.*232A>G

Variant summary

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

The NM_004048.4(B2M):​c.*232A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,188 control chromosomes in the GnomAD database, including 1,356 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 0.11 (1356 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: B2M NM_004048.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620
• Publications: 17 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]

ENSG00000294961 (HGNC:):

MIR10393 (HGNC:54002): (microRNA 10393) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004048.4. 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
	B2M	NM_004048.4	MANE Select	c.*232A>G		3_prime_UTR	Exon 4 of 4	NP_004039.1	P61769
	MIR10393	NR_162102.1		n.-20A>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B2M	ENST00000648006.3	MANE Select	c.*232A>G		3_prime_UTR	Exon 4 of 4	ENSP00000497910.1	P61769
	B2M	ENST00000906076.1		c.*224A>G		3_prime_UTR	Exon 4 of 4	ENSP00000576135.1
	B2M	ENST00000906077.1		c.*130A>G		3_prime_UTR	Exon 4 of 4	ENSP00000576136.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15988 AN: 152070 Hom.: 1338 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0673

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.0521

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0924

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 20 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

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: 0.00 AC: 0 AN: 20

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.106 AC: 16057 AN: 152188 Hom.: 1356 Cov.: 32 AF XY: 0.104 AC XY: 7756 AN XY: 74422

African (AFR) AF: 0.238 AC: 9856 AN: 41478

American (AMR) AF: 0.0671 AC: 1025 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3472

East Asian (EAS) AF: 0.0520 AC: 270 AN: 5192

South Asian (SAS) AF: 0.125 AC: 605 AN: 4830

European-Finnish (FIN) AF: 0.0162 AC: 172 AN: 10612

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0531 AC: 3608 AN: 68004

Other (OTH) AF: 0.0981 AC: 207 AN: 2110

Alfa AF: 0.0650 Hom.: 969

Bravo AF: 0.112

Asia WGS AF: 0.116 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.4
DANN	Benign	0.85
PhyloP100		0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4780; hg19: chr15-45010022; COSMIC: COSV62565223; COSMIC: COSV62565223;