chr6-31616050-T-G

Position:

• chr6-31616050-T-G

Variant summary

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

The ENST00000376049.4(AIF1):​c.-62T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,526,882 control chromosomes in the GnomAD database, including 101,604 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 0.29 (8195 hom., cov: 30)
  • Exomes 𝑓: 0.36 (93409 hom.)
• Consequence: AIF1 ENST00000376049.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIF1	NM_001623.5	c.155-54T>G		intron_variant		ENST00000376059.8
AIF1	NM_032955.3	c.-62T>G		5_prime_UTR_variant	1/3
AIF1	NM_001318970.2	c.-8-54T>G		intron_variant
AIF1	XM_005248870.5	c.155-54T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIF1	ENST00000376059.8	c.155-54T>G		intron_variant		1	NM_001623.5	P1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44181 AN: 151828 Hom.: 8190 Cov.: 30

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.361 AC: 495900 AN: 1374936 Hom.: 93409 Cov.: 55 AF XY: 0.365 AC XY: 246404 AN XY: 674756

Gnomad4 AFR exome AF: 0.0554

Gnomad4 AMR exome AF: 0.397

Gnomad4 ASJ exome AF: 0.543

Gnomad4 EAS exome AF: 0.562

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.357

GnomAD4 genome AF: 0.291 AC: 44189 AN: 151946 Hom.: 8195 Cov.: 30 AF XY: 0.295 AC XY: 21916 AN XY: 74288

Gnomad4 AFR AF: 0.0656

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.316

Alfa AF: 0.373 Hom.: 15507

Bravo AF: 0.282

Asia WGS AF: 0.426 AC: 1483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.0
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs2259571; hg19: chr6-31583827;