rs2736182

chr6-31615535-G-Achr6-31615535-G-T

Variant summary

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

The NM_001623.5(AIF1):c.40G>A(p.Gly14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 1,613,512 control chromosomes in the GnomAD database, including 2,789 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.079 (896 hom., cov: 30)
  • Exomes 𝑓: 0.032 (1893 hom.)
• Consequence: AIF1 NM_001623.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016286075).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIF1	NM_001623.5	c.40G>A	p.Gly14Arg	missense_variant	2/6	ENST00000376059.8
AIF1	XM_005248870.5	c.40G>A	p.Gly14Arg	missense_variant	2/4
AIF1	NM_001318970.2	c.-123G>A		5_prime_UTR_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIF1	ENST00000376059.8	c.40G>A	p.Gly14Arg	missense_variant	2/6	1	NM_001623.5	P1
AIF1	ENST00000337917.11	c.82G>A	p.Gly28Arg	missense_variant	2/6	1
AIF1	ENST00000466820.1	n.90G>A		non_coding_transcript_exon_variant	2/4	5
AIF1	ENST00000497362.5	n.92G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.0794 AC: 12041 AN: 151690 Hom.: 896 Cov.: 30

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.0306

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0700

Gnomad FIN AF: 0.00538

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0893

GnomAD3 exomes AF: 0.0540 AC: 13558 AN: 251276 Hom.: 810 AF XY: 0.0512 AC XY: 6954 AN XY: 135868

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.0665

Gnomad ASJ exome AF: 0.0302

Gnomad EAS exome AF: 0.147

Gnomad SAS exome AF: 0.0654

Gnomad FIN exome AF: 0.00430

Gnomad NFE exome AF: 0.0231

Gnomad OTH exome AF: 0.0496

GnomAD4 exome AF: 0.0322 AC: 47063 AN: 1461704 Hom.: 1893 Cov.: 39 AF XY: 0.0326 AC XY: 23670 AN XY: 727158

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.0688

Gnomad4 ASJ exome AF: 0.0329

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.0658

Gnomad4 FIN exome AF: 0.00586

Gnomad4 NFE exome AF: 0.0201

Gnomad4 OTH exome AF: 0.0475

GnomAD4 genome AF: 0.0794 AC: 12049 AN: 151808 Hom.: 896 Cov.: 30 AF XY: 0.0797 AC XY: 5910 AN XY: 74190

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.0719

Gnomad4 ASJ AF: 0.0306

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.0700

Gnomad4 FIN AF: 0.00538

Gnomad4 NFE AF: 0.0214

Gnomad4 OTH AF: 0.0903

Alfa AF: 0.0370 Hom.: 487

Bravo AF: 0.0900

TwinsUK AF: 0.0175 AC: 65

ALSPAC AF: 0.0205 AC: 79

ESP6500AA AF: 0.190 AC: 835

ESP6500EA AF: 0.0228 AC: 196

ExAC AF: 0.0554 AC: 6723

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.26
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.088	T;.
Eigen	Benign	0.088
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.94	D
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	0.0069	P
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Uncertain	0.34
Sift	Benign	0.056	T;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.99	D;.
Vest4		0.16
MutPred		0.20		Gain of MoRF binding (P = 0.0054);.;
MPC		0.20
ClinPred		0.075	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.086
gMVP		0.83

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: rs2736182; hg19: chr6-31583312;