rs2986425

Positions:

• chr11-34894209-A-G
• chr11-34894209-A-T

Variant summary

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

The ENST00000395787.4(APIP):​c.158+801T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,878 control chromosomes in the GnomAD database, including 10,940 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 0.37 (10940 hom., cov: 31)
• Consequence: APIP ENST00000395787.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

Genes affected

APIP (HGNC:17581): (APAF1 interacting protein) Enables identical protein binding activity; methylthioribulose 1-phosphate dehydratase activity; and zinc ion binding activity. Involved in several processes, including L-methionine salvage from methylthioadenosine; protein homotetramerization; and pyroptosis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APIP	NM_015957.4	c.158+801T>C		intron_variant		ENST00000395787.4	NP_057041.2
APIP	XM_011520154.4	c.209+801T>C		intron_variant			XP_011518456.1
APIP	XM_017017875.3	c.-59+801T>C		intron_variant			XP_016873364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APIP	ENST00000395787.4	c.158+801T>C		intron_variant		1	NM_015957.4	ENSP00000379133	P1
APIP	ENST00000527830.1	n.125-3657T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56602 AN: 151760 Hom.: 10943 Cov.: 31

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.373 AC: 56613 AN: 151878 Hom.: 10940 Cov.: 31 AF XY: 0.382 AC XY: 28362 AN XY: 74210

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.359

Alfa AF: 0.367 Hom.: 1787

Bravo AF: 0.368

Asia WGS AF: 0.594 AC: 2067 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs2986425; hg19: chr11-34915756;