chr6-31615535-G-T

Variant names:

• chr6-31615535-G-T
• rs2736182
• NM_001623.5:c.40G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001623.5(AIF1):​c.40G>T​(p.Gly14*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: AIF1 NM_001623.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49
• Publications: 31 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIF1	NM_001623.5	MANE Select	c.40G>T	p.Gly14*	stop_gained	Exon 2 of 6	NP_001614.3
	AIF1	NM_001318970.2		c.-123G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001305899.1
	AIF1	NM_001318970.2		c.-123G>T		5_prime_UTR	Exon 2 of 6	NP_001305899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIF1	ENST00000376059.8	TSL:1 MANE Select	c.40G>T	p.Gly14*	stop_gained	Exon 2 of 6	ENSP00000365227.3
	AIF1	ENST00000337917.11	TSL:1	c.82G>T	p.Gly28*	stop_gained	Exon 2 of 6	ENSP00000338776.7
	AIF1	ENST00000466820.1	TSL:5	n.90G>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 1143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	36
DANN	Uncertain	0.98
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.94	D
PhyloP100		3.5
Vest4		0.79
GERP RS		3.6
PromoterAI		-0.0092	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=38/162	disease causing (fs/PTC)

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: rs2736182; hg19: chr6-31583312;