11-34880331-G-C

Position:

• chr11-34880331-G-C

Variant summary

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

The ENST00000532428.6(APIP):​c.*41+2345C>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,038 control chromosomes in the GnomAD database, including 25,244 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 0.56 (25244 hom., cov: 32)
• Consequence: APIP ENST00000532428.6 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APIP	ENST00000532428.6	c.*41+2345C>G		intron_variant, NMD_transcript_variant		1		ENSP00000474191

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85628 AN: 151920 Hom.: 25221 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.564 AC: 85687 AN: 152038 Hom.: 25244 Cov.: 32 AF XY: 0.570 AC XY: 42360 AN XY: 74306

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.535

Alfa AF: 0.385 Hom.: 1080

Bravo AF: 0.569

Asia WGS AF: 0.689 AC: 2398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.2
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2915228; hg19: chr11-34901878;