rs1474056

Variant names:

• chr11-47611155-G-A
• rs1474056
• XM_011519959.3:c.826-4901C>T

Variant summary

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

The XM_011519959.3(MTCH2):​c.826-4901C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,214 control chromosomes in the GnomAD database, including 3,720 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 0.21 (3720 hom., cov: 32)
• Consequence: MTCH2 XM_011519959.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 13 publications found

Genes affected

MTCH2 (HGNC:17587): (mitochondrial carrier 2) This gene encodes a member of the SLC25 family of nuclear-encoded transporters that are localized in the inner mitochondrial membrane. Members of this superfamily are involved in many metabolic pathways and cell functions. Genome-wide association studies in human have identified single-nucleotide polymorphisms in several loci associated with obesity. This gene is one such locus, which is highly expressed in white adipose tissue and adipocytes, and thought to play a regulatory role in adipocyte differentiation and biology. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A recent study showed this gene to be an authentic stop codon readthrough target that can produce two isoforms from the same mRNA by use of alternative in-frame translation termination codons. [provided by RefSeq, Dec 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31253 AN: 152096 Hom.: 3723 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.205 AC: 31259 AN: 152214 Hom.: 3720 Cov.: 32 AF XY: 0.213 AC XY: 15828 AN XY: 74420

African (AFR) AF: 0.294 AC: 12195 AN: 41530

American (AMR) AF: 0.221 AC: 3374 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3472

East Asian (EAS) AF: 0.302 AC: 1564 AN: 5180

South Asian (SAS) AF: 0.161 AC: 776 AN: 4824

European-Finnish (FIN) AF: 0.267 AC: 2825 AN: 10584

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9578 AN: 68006

Other (OTH) AF: 0.164 AC: 346 AN: 2114

Alfa AF: 0.153 Hom.: 1079

Bravo AF: 0.208

Asia WGS AF: 0.198 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.6
DANN	Benign	0.78
PhyloP100		-0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1474056; hg19: chr11-47632707;