11-34882852-C-T

Position:

• chr11-34882852-C-T

Variant summary

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

The NM_015957.4(APIP):​c.630-36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,407,628 control chromosomes in the GnomAD database, including 316,135 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 0.60 (28461 hom., cov: 31)
  • Exomes 𝑓: 0.67 (287674 hom.)
• Consequence: APIP NM_015957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APIP	NM_015957.4	c.630-36G>A		intron_variant		ENST00000395787.4
APIP	XM_011520154.4	c.681-36G>A		intron_variant
APIP	XM_017017875.3	c.414-36G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APIP	ENST00000395787.4	c.630-36G>A		intron_variant		1	NM_015957.4	P1
APIP	ENST00000532428.6	c.489-36G>A		intron_variant, NMD_transcript_variant		1
APIP	ENST00000527830.1	n.596-36G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91288 AN: 151850 Hom.: 28466 Cov.: 31

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.597

GnomAD3 exomes AF: 0.643 AC: 149717 AN: 232724 Hom.: 49183 AF XY: 0.650 AC XY: 82323 AN XY: 126610

Gnomad AFR exome AF: 0.406

Gnomad AMR exome AF: 0.539

Gnomad ASJ exome AF: 0.683

Gnomad EAS exome AF: 0.751

Gnomad SAS exome AF: 0.627

Gnomad FIN exome AF: 0.656

Gnomad NFE exome AF: 0.686

Gnomad OTH exome AF: 0.648

GnomAD4 exome AF: 0.675 AC: 847080 AN: 1255660 Hom.: 287674 Cov.: 16 AF XY: 0.673 AC XY: 427266 AN XY: 634412

Gnomad4 AFR exome AF: 0.408

Gnomad4 AMR exome AF: 0.551

Gnomad4 ASJ exome AF: 0.682

Gnomad4 EAS exome AF: 0.725

Gnomad4 SAS exome AF: 0.627

Gnomad4 FIN exome AF: 0.657

Gnomad4 NFE exome AF: 0.691

Gnomad4 OTH exome AF: 0.664

GnomAD4 genome AF: 0.601 AC: 91310 AN: 151968 Hom.: 28461 Cov.: 31 AF XY: 0.602 AC XY: 44702 AN XY: 74268

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.591

Alfa AF: 0.612 Hom.: 4565

Bravo AF: 0.589

Asia WGS AF: 0.660 AC: 2296 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.014
DANN	Benign	0.73

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: rs2288667; hg19: chr11-34904399; COSMIC: COSV53506896;