rs1474056

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTCH2	XM_011519959.3	c.826-4901C>T		intron_variant	Intron 12 of 12		XP_011518261.1
MTCH2	XM_011519960.4	c.799-4901C>T		intron_variant	Intron 11 of 11		XP_011518262.1
MTCH2	XM_011519961.3	c.758-4901C>T		intron_variant	Intron 11 of 11		XP_011518263.1
MTCH2	XM_047426700.1	c.445-4901C>T		intron_variant	Intron 11 of 11		XP_047282656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.164

Alfa AF: 0.152 Hom.: 971

Bravo AF: 0.208

Asia WGS AF: 0.198 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1474056; hg19: chr11-47632707;