rs2271695

Variant names:

• chr10-70114978-G-A
• rs2271695
• NM_032797.6:c.912C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032797.6(AIFM2):​c.912C>T​(p.Ile304Ile) 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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032797.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIFM2	NM_032797.6	MANE Select	c.912C>T	p.Ile304Ile	synonymous	Exon 8 of 9	NP_116186.1
	AIFM2	NM_001198696.2		c.912C>T	p.Ile304Ile	synonymous	Exon 8 of 9	NP_001185625.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIFM2	ENST00000307864.3	TSL:1 MANE Select	c.912C>T	p.Ile304Ile	synonymous	Exon 8 of 9	ENSP00000312370.1
	AIFM2	ENST00000373248.5	TSL:1	c.912C>T	p.Ile304Ile	synonymous	Exon 7 of 9	ENSP00000362345.1
	AIFM2	ENST00000613322.4	TSL:5	c.912C>T	p.Ile304Ile	synonymous	Exon 8 of 9	ENSP00000478931.1

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

GnomAD2 exomes AF: 0.0971 AC: 24384 AN: 251032 AF XY: 0.0885

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 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

African (AFR) AF: 0.187 AC: 6246 AN: 33474

American (AMR) AF: 0.200 AC: 8921 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 3049 AN: 26134

East Asian (EAS) AF: 0.183 AC: 7268 AN: 39690

South Asian (SAS) AF: 0.0535 AC: 4610 AN: 86232

European-Finnish (FIN) AF: 0.0546 AC: 2917 AN: 53378

Middle Eastern (MID) AF: 0.0735 AC: 424 AN: 5768

European-Non Finnish (NFE) AF: 0.0582 AC: 64695 AN: 1111934

Other (OTH) AF: 0.0817 AC: 4936 AN: 60392

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

African (AFR) AF: 0.187 AC: 7753 AN: 41546

American (AMR) AF: 0.164 AC: 2512 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3472

East Asian (EAS) AF: 0.174 AC: 900 AN: 5166

South Asian (SAS) AF: 0.0561 AC: 271 AN: 4828

European-Finnish (FIN) AF: 0.0482 AC: 512 AN: 10624

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0614 AC: 4178 AN: 68030

Other (OTH) AF: 0.114 AC: 242 AN: 2114

Alfa AF: 0.0808 Hom.: 984

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.70
DANN	Benign	0.93
PhyloP100		-1.8
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: rs2271695; hg19: chr10-71874734; COSMIC: COSV57158523; COSMIC: COSV57158523;