rs2576581

Positions:

• chr8-56453391-G-A
• chr8-56453391-G-C
• chr8-56453391-G-T

Variant summary

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

The NR_125813.1(PENK-AS1):​n.694+6891G>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 0.416 in 152,008 control chromosomes in the GnomAD database, including 13,764 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 0.42 (13764 hom., cov: 33)
• Consequence: PENK-AS1 NR_125813.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PENK-AS1	NR_125813.1	n.694+6891G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PENK-AS1	ENST00000662661.1	n.264+6891G>A		intron_variant, non_coding_transcript_variant
PENK-AS1	ENST00000518662.5	n.694+6891G>A		intron_variant, non_coding_transcript_variant		2
PENK-AS1	ENST00000685796.1	n.657+6891G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63198 AN: 151890 Hom.: 13753 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.416 AC: 63230 AN: 152008 Hom.: 13764 Cov.: 33 AF XY: 0.419 AC XY: 31165 AN XY: 74304

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.414

Alfa AF: 0.457 Hom.: 15791

Bravo AF: 0.398

Asia WGS AF: 0.477 AC: 1651 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.66
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2576581; hg19: chr8-57365950;