Genetic Variant NM_001623.5: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

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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