rs2271695

Positions:

• chr10-70114978-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032797.6(AIFM2):​c.912C>T​(p.Ile304=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0743 in 1,613,952 control chromosomes in the GnomAD database, including 6,060 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 (1265 hom., cov: 33)
  • Exomes 𝑓: 0.071 (4795 hom.)
• Consequence: AIFM2 NM_032797.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

Genes affected

AIFM2 (HGNC:21411): (apoptosis inducing factor mitochondria associated 2) This gene encodes a flavoprotein oxidoreductase that binds single stranded DNA and is thought to contribute to apoptosis in the presence of bacterial and viral DNA. The expression of this gene is also found to be induced by tumor suppressor protein p53 in colon cancer cells. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-1.77 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIFM2	NM_032797.6	c.912C>T	p.Ile304=	synonymous_variant	8/9	ENST00000307864.3
AIFM2	NM_001198696.2	c.912C>T	p.Ile304=	synonymous_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIFM2	ENST00000307864.3	c.912C>T	p.Ile304=	synonymous_variant	8/9	1	NM_032797.6	P1
AIFM2	ENST00000373248.5	c.912C>T	p.Ile304=	synonymous_variant	7/9	1		P1
AIFM2	ENST00000613322.4	c.912C>T	p.Ile304=	synonymous_variant	8/9	5		P1
AIFM2	ENST00000482166.1	n.749C>T		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16793 AN: 152166 Hom.: 1259 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.0482

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0614

Gnomad OTH AF: 0.116

GnomAD3 exomes AF: 0.0971 AC: 24384 AN: 251032 Hom.: 1690 AF XY: 0.0885 AC XY: 12007 AN XY: 135718

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.160

Gnomad SAS exome AF: 0.0501

Gnomad FIN exome AF: 0.0537

Gnomad NFE exome AF: 0.0614

Gnomad OTH exome AF: 0.0929

GnomAD4 exome AF: 0.0705 AC: 103066 AN: 1461668 Hom.: 4795 Cov.: 31 AF XY: 0.0689 AC XY: 50101 AN XY: 727132

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.0535

Gnomad4 FIN exome AF: 0.0546

Gnomad4 NFE exome AF: 0.0582

Gnomad4 OTH exome AF: 0.0817

GnomAD4 genome AF: 0.110 AC: 16817 AN: 152284 Hom.: 1265 Cov.: 33 AF XY: 0.111 AC XY: 8248 AN XY: 74450

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.0561

Gnomad4 FIN AF: 0.0482

Gnomad4 NFE AF: 0.0614

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0760 Hom.: 669

Bravo AF: 0.124

Asia WGS AF: 0.126 AC: 436 AN: 3478

EpiCase AF: 0.0582

EpiControl AF: 0.0614

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.70
DANN	Benign	0.93

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

LitVar

Other links and lift over

dbSNP: rs2271695; hg19: chr10-71874734; COSMIC: COSV57158523; COSMIC: COSV57158523;