rs2857597

Variant names:

• chr6-31617223-T-A
• rs2857597
• NM_001623.5:c.*323T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31617223-T-A
• chr6-31617223-T-G

Variant summary

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

The NM_001623.5(AIF1):​c.*323T>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,042 control chromosomes in the GnomAD database, including 42,428 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 0.74 (42428 hom., cov: 31)
• Consequence: AIF1 NM_001623.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

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 (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIF1	NM_001623.5	c.*323T>A		downstream_gene_variant		ENST00000376059.8	NP_001614.3
AIF1	NM_001318970.2	c.*323T>A		downstream_gene_variant			NP_001305899.1
AIF1	NM_032955.3	c.*323T>A		downstream_gene_variant			NP_116573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIF1	ENST00000376059.8	c.*323T>A		downstream_gene_variant		1	NM_001623.5	ENSP00000365227.3
AIF1	ENST00000337917.11	c.*323T>A		downstream_gene_variant		1		ENSP00000338776.7
AIF1	ENST00000376049.4	c.*323T>A		downstream_gene_variant		1		ENSP00000365217.4
AIF1	ENST00000466820.1	n.*202T>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113029 AN: 151924 Hom.: 42399 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.755

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.744 AC: 113102 AN: 152042 Hom.: 42428 Cov.: 31 AF XY: 0.751 AC XY: 55793 AN XY: 74318

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.759

Alfa AF: 0.765 Hom.: 24906

Bravo AF: 0.737

Asia WGS AF: 0.903 AC: 3139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2857597; hg19: chr6-31585000;