8-56511114-G-A

Position:

• chr8-56511114-G-A

Variant summary

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

The NR_125813.1(PENK-AS1):​n.827+14759G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,106 control chromosomes in the GnomAD database, including 43,073 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 0.75 (43073 hom., cov: 32)
• Consequence: PENK-AS1 NR_125813.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464

Genes affected

LINC00968 (HGNC:48727): (long intergenic non-protein coding RNA 968)

PENK-AS1 (HGNC:55519): (PENK antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PENK-AS1	NR_125813.1	n.827+14759G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINC00968	ENST00000524338.3	n.818+9007C>T		intron_variant, non_coding_transcript_variant		2
PENK-AS1	ENST00000662661.1	n.397+14759G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114302 AN: 151988 Hom.: 43042 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.752 AC: 114389 AN: 152106 Hom.: 43073 Cov.: 32 AF XY: 0.752 AC XY: 55885 AN XY: 74356

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.760

Gnomad4 ASJ AF: 0.789

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.753

Alfa AF: 0.759 Hom.: 7472

Bravo AF: 0.746

Asia WGS AF: 0.783 AC: 2726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2670028; hg19: chr8-57423673;