ENST00000376049.4:c.-62T>G

Variant names:

• chr6-31616050-T-G
• rs2259571
• ENST00000376049.4:c.-62T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 51 publications found

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]

ENSG00000289375 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000376049.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIF1	NM_001623.5	MANE Select	c.155-54T>G		intron	N/A	NP_001614.3
	AIF1	NM_032955.3		c.-62T>G		5_prime_UTR	Exon 1 of 3	NP_116573.1
	AIF1	NM_001318970.2		c.-8-54T>G		intron	N/A	NP_001305899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIF1	ENST00000376049.4	TSL:1	c.-62T>G		5_prime_UTR	Exon 1 of 3	ENSP00000365217.4
	AIF1	ENST00000376059.8	TSL:1 MANE Select	c.155-54T>G		intron	N/A	ENSP00000365227.3
	AIF1	ENST00000337917.11	TSL:1	c.197-54T>G		intron	N/A	ENSP00000338776.7

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

African (AFR) AF: 0.0554 AC: 1699 AN: 30680

American (AMR) AF: 0.397 AC: 12438 AN: 31362

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 11037 AN: 20316

East Asian (EAS) AF: 0.562 AC: 21894 AN: 38968

South Asian (SAS) AF: 0.428 AC: 30556 AN: 71444

European-Finnish (FIN) AF: 0.317 AC: 15656 AN: 49420

Middle Eastern (MID) AF: 0.440 AC: 2273 AN: 5164

European-Non Finnish (NFE) AF: 0.355 AC: 380136 AN: 1070990

Other (OTH) AF: 0.357 AC: 20211 AN: 56592

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

African (AFR) AF: 0.0656 AC: 2718 AN: 41460

American (AMR) AF: 0.339 AC: 5170 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1900 AN: 3470

East Asian (EAS) AF: 0.573 AC: 2952 AN: 5150

South Asian (SAS) AF: 0.438 AC: 2106 AN: 4806

European-Finnish (FIN) AF: 0.316 AC: 3340 AN: 10568

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24739 AN: 67916

Other (OTH) AF: 0.316 AC: 668 AN: 2114

Alfa AF: 0.346 Hom.: 22576

Bravo AF: 0.282

Asia WGS AF: 0.426 AC: 1483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.0
DANN	Benign	0.68
PhyloP100		-0.53
PromoterAI		0.10	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2259571; hg19: chr6-31583827;