rs2609997

Positions:

• chr8-56447926-T-C

Variant summary

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

The ENST00000518662.5(PENK-AS1):​n.694+1426T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,120 control chromosomes in the GnomAD database, including 11,075 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 0.35 (11075 hom., cov: 32)
• Consequence: PENK-AS1 ENST00000518662.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

Genes affected

PENK-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PENK-AS1	NR_125813.1	n.694+1426T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PENK-AS1	ENST00000518662.5	n.694+1426T>C		intron_variant		2
PENK-AS1	ENST00000662661.1	n.264+1426T>C		intron_variant
PENK-AS1	ENST00000685796.1	n.657+1426T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53137 AN: 152002 Hom.: 11072 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.349 AC: 53148 AN: 152120 Hom.: 11075 Cov.: 32 AF XY: 0.353 AC XY: 26228 AN XY: 74346

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.366

Alfa AF: 0.431 Hom.: 13913

Bravo AF: 0.324

Asia WGS AF: 0.406 AC: 1413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2609997; hg19: chr8-57360485;