chr9-131096861-C-A

Variant names:

• chr9-131096861-C-A
• rs774289256
• NM_031426.4:c.91C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_031426.4(AIF1L):​c.91C>A​(p.Arg31Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AIF1L NM_031426.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0008941
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 0 publications found

Genes affected

AIF1L (HGNC:28904): (allograft inflammatory factor 1 like) Enables actin filament binding activity. Predicted to be involved in actin filament bundle assembly and ruffle assembly. Located in actin cytoskeleton and focal adhesion. Colocalizes with actin filament. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP7: Synonymous conserved (PhyloP=0.223 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031426.4. 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
	AIF1L	NM_031426.4	MANE Select	c.91C>A	p.Arg31Arg	splice_region synonymous	Exon 2 of 6	NP_113614.1	Q9BQI0-1
	AIF1L	NM_001185095.2		c.91C>A	p.Arg31Arg	splice_region synonymous	Exon 2 of 7	NP_001172024.1	Q9BQI0-2
	AIF1L	NM_001185096.2		c.91C>A	p.Arg31Arg	splice_region synonymous	Exon 2 of 6	NP_001172025.1	Q9BQI0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIF1L	ENST00000247291.8	TSL:1 MANE Select	c.91C>A	p.Arg31Arg	splice_region synonymous	Exon 2 of 6	ENSP00000247291.3	Q9BQI0-1
	AIF1L	ENST00000372302.5	TSL:2	c.91C>A	p.Arg31Arg	splice_region synonymous	Exon 2 of 6	ENSP00000361376.1	Q9BQI0-3
	AIF1L	ENST00000372300.5	TSL:1	c.91C>A	p.Arg31Arg	splice_region synonymous	Exon 2 of 6	ENSP00000361374.1	Q9BQI0-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1382484 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 682216

African (AFR) AF: 0.00 AC: 0 AN: 29672

American (AMR) AF: 0.00 AC: 0 AN: 33784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24682

East Asian (EAS) AF: 0.00 AC: 0 AN: 33608

South Asian (SAS) AF: 0.00 AC: 0 AN: 77692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5450

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073998

Other (OTH) AF: 0.00 AC: 0 AN: 57362

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.21
CADD	Benign	17
DANN	Benign	0.94
PhyloP100		0.22
PromoterAI		0.0087	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00089
dbscSNV1_RF	Benign	0.018
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: rs774289256; hg19: chr9-133972248;