6-31616154-C-A

Variant names:

• chr6-31616154-C-A
• rs2269475
• NM_001623.5:c.196+9C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001623.5(AIF1):​c.196+9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,044 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AIF1 NM_001623.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

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.196+9C>A		intron	N/A	NP_001614.3
	AIF1	NM_001318970.2		c.34+9C>A		intron	N/A	NP_001305899.1	P55008-2
	AIF1	NM_032955.3		c.34+9C>A		intron	N/A	NP_116573.1	I3WTX1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIF1	ENST00000376059.8	TSL:1 MANE Select	c.196+9C>A		intron	N/A	ENSP00000365227.3	P55008-1
	AIF1	ENST00000337917.11	TSL:1	c.238+9C>A		intron	N/A	ENSP00000338776.7	Q5STX8
	AIF1	ENST00000376049.4	TSL:1	c.34+9C>A		intron	N/A	ENSP00000365217.4	P55008-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458044 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 725118

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25828

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 85826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110324

Other (OTH) AF: 0.00 AC: 0 AN: 60236

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.2
DANN	Benign	0.70
PhyloP100		-0.25
PromoterAI		-0.092	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2269475; hg19: chr6-31583931;