rs10489846

Positions:

• chr1-159116921-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000411768.2(AIM2):​c.-21+5318T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0864 in 152,164 control chromosomes in the GnomAD database, including 1,411 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 0.086 (1411 hom., cov: 31)
• Consequence: AIM2 ENST00000411768.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

Genes affected

AIM2 (HGNC:357): (absent in melanoma 2) AIM2 is a member of the IFI20X /IFI16 family. It plays a putative role in tumorigenic reversion and may control cell proliferation. Interferon-gamma induces expression of AIM2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIM2	XM_047434808.1	c.-21+5318T>C		intron_variant
AIM2	XM_047434809.1	c.-124+6599T>C		intron_variant
AIM2	XR_007064924.1	n.438+5318T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIM2	ENST00000368129.3	c.-16+23510T>C		intron_variant		2
AIM2	ENST00000411768.2	c.-21+5318T>C		intron_variant		5		P1
AIM2	ENST00000695579.1	c.-16+15322T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0862 AC: 13104 AN: 152042 Hom.: 1404 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0340

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00991

Gnomad OTH AF: 0.0680

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0864 AC: 13148 AN: 152164 Hom.: 1411 Cov.: 31 AF XY: 0.0853 AC XY: 6351 AN XY: 74438

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.0490

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0340

Gnomad4 FIN AF: 0.00330

Gnomad4 NFE AF: 0.00991

Gnomad4 OTH AF: 0.0678

Alfa AF: 0.0541 Hom.: 113

Bravo AF: 0.0984

Asia WGS AF: 0.0840 AC: 294 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.085
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10489846; hg19: chr1-159086711;