chr6-31615389-G-A

Variant names:

• chr6-31615389-G-A
• rs4711274
• NM_001623.5:c.25+35G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001623.5(AIF1):​c.25+35G>A 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 1,612,118 control chromosomes in the GnomAD database, including 17,003 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 (1830 hom., cov: 31)
  • Exomes 𝑓: 0.13 (15173 hom.)
• Consequence: AIF1 NM_001623.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001623.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIF1	NM_001623.5	MANE Select	c.25+35G>A		intron	N/A	NP_001614.3
	AIF1	NM_001318970.2		c.-138+96G>A		intron	N/A	NP_001305899.1	P55008-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIF1	ENST00000376059.8	TSL:1 MANE Select	c.25+35G>A		intron	N/A	ENSP00000365227.3	P55008-1
	AIF1	ENST00000337917.11	TSL:1	c.67+96G>A		intron	N/A	ENSP00000338776.7	Q5STX8
	AIF1	ENST00000889060.1		c.25+35G>A		intron	N/A	ENSP00000559119.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21424 AN: 151958 Hom.: 1826 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0973

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.109

GnomAD2 exomes AF: 0.151 AC: 37856 AN: 251180 AF XY: 0.143

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.233

Gnomad ASJ exome AF: 0.0297

Gnomad EAS exome AF: 0.140

Gnomad FIN exome AF: 0.314

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.135

GnomAD4 exome AF: 0.134 AC: 195719 AN: 1460042 Hom.: 15173 Cov.: 38 AF XY: 0.131 AC XY: 95384 AN XY: 726414

African (AFR) AF: 0.0907 AC: 3034 AN: 33454

American (AMR) AF: 0.223 AC: 9977 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0313 AC: 817 AN: 26122

East Asian (EAS) AF: 0.215 AC: 8509 AN: 39660

South Asian (SAS) AF: 0.0905 AC: 7804 AN: 86210

European-Finnish (FIN) AF: 0.311 AC: 16609 AN: 53390

Middle Eastern (MID) AF: 0.0434 AC: 250 AN: 5762

European-Non Finnish (NFE) AF: 0.127 AC: 141403 AN: 1110426

Other (OTH) AF: 0.121 AC: 7316 AN: 60318

GnomAD4 genome AF: 0.141 AC: 21451 AN: 152076 Hom.: 1830 Cov.: 31 AF XY: 0.149 AC XY: 11061 AN XY: 74344

African (AFR) AF: 0.103 AC: 4273 AN: 41492

American (AMR) AF: 0.189 AC: 2892 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 107 AN: 3470

East Asian (EAS) AF: 0.147 AC: 759 AN: 5170

South Asian (SAS) AF: 0.0972 AC: 469 AN: 4824

European-Finnish (FIN) AF: 0.332 AC: 3504 AN: 10562

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9083 AN: 67988

Other (OTH) AF: 0.108 AC: 227 AN: 2098

Alfa AF: 0.137 Hom.: 1894

Bravo AF: 0.131

Asia WGS AF: 0.140 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.58
PhyloP100		0.34
PromoterAI		-0.062	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4711274; hg19: chr6-31583166; COSMIC: COSV61962464; COSMIC: COSV61962464;