rs7908957

Positions:

• chr10-70113825-G-A
• chr10-70113825-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000307864.3(AIFM2):​c.*353C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 202,254 control chromosomes in the GnomAD database, including 6,769 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 0.25 (5944 hom., cov: 32)
  • Exomes 𝑓: 0.16 (825 hom.)
• Consequence: AIFM2 ENST00000307864.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIFM2	NM_032797.6	c.*353C>T		3_prime_UTR_variant	9/9	ENST00000307864.3	NP_116186.1
AIFM2	NM_001198696.2	c.*353C>T		3_prime_UTR_variant	9/9		NP_001185625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIFM2	ENST00000307864.3	c.*353C>T		3_prime_UTR_variant	9/9	1	NM_032797.6	ENSP00000312370	P1
AIFM2	ENST00000373248.5	c.*33+320C>T		intron_variant		1		ENSP00000362345	P1
AIFM2	ENST00000613322.4	c.*353C>T		3_prime_UTR_variant	9/9	5		ENSP00000478931	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37644 AN: 151818 Hom.: 5937 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.157 AC: 7921 AN: 50318 Hom.: 825 Cov.: 0 AF XY: 0.163 AC XY: 4241 AN XY: 26016

Gnomad4 AFR exome AF: 0.419

Gnomad4 AMR exome AF: 0.228

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.248 AC: 37688 AN: 151936 Hom.: 5944 Cov.: 32 AF XY: 0.252 AC XY: 18714 AN XY: 74264

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.240

Alfa AF: 0.172 Hom.: 1136

Bravo AF: 0.261

Asia WGS AF: 0.333 AC: 1159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.39

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: rs7908957; hg19: chr10-71873581;