dbSNP rs4711274: AIF1:c.25+35G>A (chr6-31615389-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001623.5(AIF1):c.25+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,612,118 control chromosomes in the GnomAD database, including 17,003 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 0.14 ( 1830 hom., cov: 31)

Exomes 𝑓: 0.13 ( 15173 hom. )

Consequence

AIF1
NM_001623.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.341

Publications

8 publications found

Variant links:

Genes affected

AIF1 (HGNC:352): (allograft inflammatory factor 1) This gene encodes a protein that binds actin and calcium. This gene is induced by cytokines and interferon and may promote macrophage activation and growth of vascular smooth muscle cells and T-lymphocytes. Polymorphisms in this gene may be associated with systemic sclerosis. Alternative splicing results in multiple transcript variants, but the full-length and coding nature of some of these variants is not certain. [provided by RefSeq, Jan 2016]

AIF1 links:

ENSG00000289375 (HGNC:):

ENSG00000289375 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AIF1	NM_001623.5 link	c.25+35G>A	intron_variant	Intron 1 of 5	ENST00000376059.8	NP_001614.3	P55008-1Q4V347
AIF1	NM_001318970.2 link	c.-138+96G>A	intron_variant	Intron 1 of 5		NP_001305899.1	P55008-2I3WTX1
AIF1	XM_005248870.5 link	c.25+35G>A	intron_variant	Intron 1 of 3		XP_005248927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIF1	ENST00000376059.8 link	c.25+35G>A		intron_variant	Intron 1 of 5	1	NM_001623.5	ENSP00000365227.3		P55008-1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21424

AN:

151958

Hom.:

1826

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.0973

Gnomad FIN

AF:

0.332

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.109

GnomAD2 exomes

AF:

0.151

AC:

37856

AN:

251180

AF XY:

0.143

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.0297

Gnomad EAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.314

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.134

AC:

195719

AN:

1460042

Hom.:

15173

Cov.:

AF XY:

0.131

AC XY:

95384

AN XY:

726414

show subpopulations

African (AFR)

AF:

0.0907

AC:

3034

AN:

33454

American (AMR)

AF:

0.223

AC:

9977

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0313

AC:

817

AN:

26122

East Asian (EAS)

AF:

0.215

AC:

8509

AN:

39660

South Asian (SAS)

AF:

0.0905

AC:

7804

AN:

86210

European-Finnish (FIN)

AF:

0.311

AC:

16609

AN:

53390

Middle Eastern (MID)

AF:

0.0434

AC:

250

AN:

5762

European-Non Finnish (NFE)

AF:

0.127

AC:

141403

AN:

1110426

Other (OTH)

AF:

0.121

AC:

7316

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

9548

19095

28643

38190

47738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5114

10228

15342

20456

25570

<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:

0.141

AC:

21451

AN:

152076

Hom.:

1830

Cov.:

AF XY:

0.149

AC XY:

11061

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.103

AC:

4273

AN:

41492

American (AMR)

AF:

0.189

AC:

2892

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

107

AN:

3470

East Asian (EAS)

AF:

0.147

AC:

759

AN:

5170

South Asian (SAS)

AF:

0.0972

AC:

469

AN:

4824

European-Finnish (FIN)

AF:

0.332

AC:

3504

AN:

10562

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.134

AC:

9083

AN:

67988

Other (OTH)

AF:

0.108

AC:

227

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

895

1790

2684

3579

4474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<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:

0.137

Hom.:

1894

Bravo

AF:

0.131

Asia WGS

AF:

0.140

AC:

487

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.6

(source)

DANN

Benign

0.58

PhyloP100

0.34

PromoterAI

-0.062

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over