rs6438759

Positions:

• chr3-122721219-A-G
• chr3-122721219-A-T

Variant summary

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

The NM_017554.3(PARP14):​c.4941+831A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 233,872 control chromosomes in the GnomAD database, including 92,558 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 0.89 (59770 hom., cov: 31)
  • Exomes 𝑓: 0.89 (32788 hom.)
• Consequence: PARP14 NM_017554.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318

Genes affected

PARP14 (HGNC:29232): (poly(ADP-ribose) polymerase family member 14) This gene encodes a member of the poly(ADP-ribose) polymerase (PARP) protein family. The encoded anti-apoptotic protein may regulate aerobic glycolysis and promote survival of cancer cells. Increased expression of this gene has been reported in a variety of tumor types. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP14	NM_017554.3	c.4941+831A>G		intron_variant		ENST00000474629.7	NP_060024.2
PARP14	XR_007095695.1	n.5118A>G		non_coding_transcript_exon_variant	16/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP14	ENST00000474629.7	c.4941+831A>G		intron_variant		1	NM_017554.3	ENSP00000418194	P1
PARP14	ENST00000474669.1	n.3801A>G		non_coding_transcript_exon_variant	10/10	1
PARP14	ENST00000460683.1	c.*729A>G		3_prime_UTR_variant, NMD_transcript_variant	12/14	5		ENSP00000420649
PARP14	ENST00000649945.1	c.*1816+831A>G		intron_variant, NMD_transcript_variant				ENSP00000497854

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134744 AN: 152050 Hom.: 59715 Cov.: 31

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.885

GnomAD4 exome AF: 0.895 AC: 73122 AN: 81704 Hom.: 32788 Cov.: 0 AF XY: 0.900 AC XY: 40085 AN XY: 44518

Gnomad4 AFR exome AF: 0.860

Gnomad4 AMR exome AF: 0.921

Gnomad4 ASJ exome AF: 0.887

Gnomad4 EAS exome AF: 0.981

Gnomad4 SAS exome AF: 0.937

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.879

Gnomad4 OTH exome AF: 0.893

GnomAD4 genome AF: 0.886 AC: 134858 AN: 152168 Hom.: 59770 Cov.: 31 AF XY: 0.888 AC XY: 66039 AN XY: 74382

Gnomad4 AFR AF: 0.868

Gnomad4 AMR AF: 0.914

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.982

Gnomad4 SAS AF: 0.949

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.880

Gnomad4 OTH AF: 0.886

Alfa AF: 0.888 Hom.: 27298

Bravo AF: 0.888

Asia WGS AF: 0.956 AC: 3326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.2
DANN	Benign	0.65

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: rs6438759; hg19: chr3-122440066;