1-159068562-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004833.3(AIM2):c.396+6A>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,610,286 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (21 hom.)
• Consequence: AIM2 NM_004833.3 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00003995
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.360

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-159068562-T-A is Benign according to our data. Variant chr1-159068562-T-A is described in ClinVar as [Benign]. Clinvar id is 780269.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00802 (1221/152320) while in subpopulation AFR AF= 0.0275 (1144/41564). AF 95% confidence interval is 0.0262. There are 11 homozygotes in gnomad4. There are 568 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIM2	NM_004833.3	c.396+6A>T		splice_donor_region_variant, intron_variant		ENST00000368130.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIM2	ENST00000368130.9	c.396+6A>T		splice_donor_region_variant, intron_variant		1	NM_004833.3	P1

Frequencies

GnomAD3 genomes AF: 0.00802 AC: 1220 AN: 152202 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00192 AC: 474 AN: 247496 Hom.: 12 AF XY: 0.00141 AC XY: 189 AN XY: 133948

Gnomad AFR exome AF: 0.0267

Gnomad AMR exome AF: 0.00118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000499

GnomAD4 exome AF: 0.000789 AC: 1151 AN: 1457966 Hom.: 21 Cov.: 30 AF XY: 0.000666 AC XY: 483 AN XY: 725296

Gnomad4 AFR exome AF: 0.0299

Gnomad4 AMR exome AF: 0.00128

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.00802 AC: 1221 AN: 152320 Hom.: 11 Cov.: 32 AF XY: 0.00763 AC XY: 568 AN XY: 74490

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00237 Hom.: 1

Bravo AF: 0.00926

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.3
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000040
dbscSNV1_RF	Benign	0.010
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

Publications

LitVar

Other links and lift over

dbSNP: rs114667580; hg19: chr1-159038352;