dbSNP rs2271695: AIFM2:p.Ile304Ile (chr10-70114978-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.77

Variant links:

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]

AIFM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIFM2	NM_032797.6 link	c.912C>T	p.Ile304Ile	synonymous_variant	Exon 8 of 9	ENST00000307864.3	NP_116186.1	Q9BRQ8-1
AIFM2	NM_001198696.2 link	c.912C>T	p.Ile304Ile	synonymous_variant	Exon 8 of 9		NP_001185625.1	Q9BRQ8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AIFM2	ENST00000307864.3 link	c.912C>T	p.Ile304Ile	synonymous_variant	Exon 8 of 9	1	NM_032797.6	ENSP00000312370.1	Q9BRQ8-1
AIFM2	ENST00000373248.5 link	c.912C>T	p.Ile304Ile	synonymous_variant	Exon 7 of 9	1		ENSP00000362345.1	Q9BRQ8-1
AIFM2	ENST00000613322.4 link	c.912C>T	p.Ile304Ile	synonymous_variant	Exon 8 of 9	5		ENSP00000478931.1	Q9BRQ8-1
AIFM2	ENST00000482166.1 link	n.749C>T		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16793

AN:

152166

Hom.:

1259

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0689

AC XY:

50101

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.187

AC:

6246

AN:

33474

Gnomad4 AMR exome

AF:

0.200

AC:

8921

AN:

44666

Gnomad4 ASJ exome

AF:

0.117

AC:

3049

AN:

26134

Gnomad4 EAS exome

AF:

0.183

AC:

7268

AN:

39690

Gnomad4 SAS exome

AF:

0.0535

AC:

4610

AN:

86232

Gnomad4 FIN exome

AF:

0.0546

AC:

2917

AN:

53378

Gnomad4 NFE exome

AF:

0.0582

AC:

64695

AN:

1111934

Gnomad4 Remaining exome

AF:

0.0817

AC:

4936

AN:

60392

Heterozygous variant carriers

6185

12370

18556

24741

30926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

2664

5328

7992

10656

13320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.110

AC:

16817

AN:

152284

Hom.:

1265

Cov.:

AF XY:

0.111

AC XY:

8248

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.187

AC:

0.186612

AN:

0.186612

Gnomad4 AMR

AF:

0.164

AC:

0.164204

AN:

0.164204

Gnomad4 ASJ

AF:

0.116

AC:

0.116359

AN:

0.116359

Gnomad4 EAS

AF:

0.174

AC:

0.174216

AN:

0.174216

Gnomad4 SAS

AF:

0.0561

AC:

0.0561309

AN:

0.0561309

Gnomad4 FIN

AF:

0.0482

AC:

0.0481928

AN:

0.0481928

Gnomad4 NFE

AF:

0.0614

AC:

0.0614141

AN:

0.0614141

Gnomad4 OTH

AF:

0.114

AC:

0.114475

AN:

0.114475

Heterozygous variant carriers

743

1486

2230

2973

3716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.70

DANN

Benign

0.93

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over