15-72259371-C-T

Variant names:

• chr15-72259371-C-T
• rs11637611
• NM_001323532.2:c.810+237G>A

Variant summary

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

The NM_001323532.2(PARP6):​c.810+237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,118 control chromosomes in the GnomAD database, including 31,423 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 0.63 (31423 hom., cov: 32)
• Consequence: PARP6 NM_001323532.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.784

Genes affected

PARP6 (HGNC:26921): (poly(ADP-ribose) polymerase family member 6) Enables protein ADP-ribosylase activity. Involved in protein auto-ADP-ribosylation and protein mono-ADP-ribosylation. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARP6	NM_001323532.2	c.810+237G>A		intron_variant	Intron 11 of 23	ENST00000569795.6	NP_001310461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARP6	ENST00000569795.6	c.810+237G>A		intron_variant	Intron 11 of 23	5	NM_001323532.2	ENSP00000456348.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95176 AN: 152000 Hom.: 31429 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.626 AC: 95197 AN: 152118 Hom.: 31423 Cov.: 32 AF XY: 0.627 AC XY: 46584 AN XY: 74352

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.636

Alfa AF: 0.712 Hom.: 17964

Bravo AF: 0.609

Asia WGS AF: 0.471 AC: 1640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.61
DANN	Benign	0.70

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: rs11637611; hg19: chr15-72551712; COSMIC: COSV53004821; COSMIC: COSV53004821;