rs2269475

Positions:

• chr6-31616154-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIF1	NM_001623.5	c.196+9C>T		intron_variant		ENST00000376059.8	NP_001614.3
AIF1	XM_005248870.5	c.205C>T	p.Arg69Trp	missense_variant	4/4		XP_005248927.1
AIF1	NM_001318970.2	c.34+9C>T		intron_variant			NP_001305899.1
AIF1	NM_032955.3	c.34+9C>T		intron_variant			NP_116573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIF1	ENST00000376059.8	c.196+9C>T		intron_variant		1	NM_001623.5	ENSP00000365227	P1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21372 AN: 151994 Hom.: 1801 Cov.: 31

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

GnomAD3 exomes AF: 0.152 AC: 36990 AN: 243978 Hom.: 3540 AF XY: 0.144 AC XY: 19108 AN XY: 132894

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 SAS exome AF: 0.0915

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.: 37 AF XY: 0.131 AC XY: 95226 AN XY: 725038

Gnomad4 AFR exome AF: 0.0907

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.0304

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.0907

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.141 AC: 21397 AN: 152112 Hom.: 1804 Cov.: 31 AF XY: 0.148 AC XY: 11028 AN XY: 74384

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.0978

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.108

Alfa AF: 0.124 Hom.: 2748

Bravo AF: 0.131

Asia WGS AF: 0.140 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.7
DANN	Benign	0.73

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: rs2269475; hg19: chr6-31583931; COSMIC: COSV61962470; COSMIC: COSV61962470;