Genetic Variant AIF1:c.196+9C>T (chr6-31616154-C-T) – 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.196+9C>T 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 1,610,020 control chromosomes in the GnomAD database, including 16,830 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 ( 1804 hom., cov: 31)

Exomes 𝑓: 0.13 ( 15026 hom. )

Consequence

AIF1
NM_001623.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.246

Publications

64 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=-0.76).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001623.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AIF1	NM_001623.5	MANE Select	c.196+9C>T	intron	N/A	NP_001614.3
AIF1	NM_001318970.2		c.34+9C>T	intron	N/A	NP_001305899.1	P55008-2
AIF1	NM_032955.3		c.34+9C>T	intron	N/A	NP_116573.1	I3WTX1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AIF1	ENST00000376059.8	TSL:1 MANE Select	c.196+9C>T	intron	N/A	ENSP00000365227.3	P55008-1
AIF1	ENST00000337917.11	TSL:1	c.238+9C>T	intron	N/A	ENSP00000338776.7	Q5STX8
AIF1	ENST00000376049.4	TSL:1	c.34+9C>T	intron	N/A	ENSP00000365217.4	P55008-2

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21372

AN:

151994

Hom.:

1801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.0980

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.109

GnomAD2 exomes

AF:

0.152

AC:

36990

AN:

243978

AF XY:

0.144

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.234

Gnomad ASJ exome

AF:

0.0289

Gnomad EAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.313

Gnomad NFE exome

AF:

0.131

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.134

AC:

195499

AN:

1457908

Hom.:

15026

Cov.:

AF XY:

0.131

AC XY:

95226

AN XY:

725038

show subpopulations

African (AFR)

AF:

0.0907

AC:

3030

AN:

33424

American (AMR)

AF:

0.223

AC:

9905

AN:

44352

Ashkenazi Jewish (ASJ)

AF:

0.0304

AC:

786

AN:

25826

East Asian (EAS)

AF:

0.214

AC:

8497

AN:

39644

South Asian (SAS)

AF:

0.0907

AC:

7784

AN:

85820

European-Finnish (FIN)

AF:

0.310

AC:

16316

AN:

52630

Middle Eastern (MID)

AF:

0.0433

AC:

249

AN:

5746

European-Non Finnish (NFE)

AF:

0.128

AC:

141625

AN:

1110236

Other (OTH)

AF:

0.121

AC:

7307

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

9950

19901

29851

39802

49752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5142

10284

15426

20568

25710

<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:

21397

AN:

152112

Hom.:

1804

Cov.:

AF XY:

0.148

AC XY:

11028

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.103

AC:

4259

AN:

41510

American (AMR)

AF:

0.189

AC:

2895

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0297

AC:

103

AN:

3470

East Asian (EAS)

AF:

0.147

AC:

760

AN:

5174

South Asian (SAS)

AF:

0.0978

AC:

472

AN:

4824

European-Finnish (FIN)

AF:

0.329

AC:

3477

AN:

10564

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.133

AC:

9065

AN:

67972

Other (OTH)

AF:

0.108

AC:

228

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

890

1781

2671

3562

4452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<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:

0.130

Hom.:

6313

Bravo

AF:

0.131

Asia WGS

AF:

0.140

AC:

485

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.7

(source)

DANN

Benign

0.73

PhyloP100

-0.25

PromoterAI

-0.11

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over