chr3-122721219-A-G

Variant names:

• chr3-122721219-A-G
• rs6438759
• ENST00000474669.1:n.3801A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000474669.1(PARP14):​n.3801A>G variant causes a non coding transcript exon 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 ENST00000474669.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000474669.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP14	NM_017554.3	MANE Select	c.4941+831A>G		intron	N/A	NP_060024.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARP14	ENST00000474669.1	TSL:1	n.3801A>G		non_coding_transcript_exon	Exon 10 of 10
	PARP14	ENST00000474629.7	TSL:1 MANE Select	c.4941+831A>G		intron	N/A	ENSP00000418194.2
	PARP14	ENST00000460683.1	TSL:5	n.*729A>G		non_coding_transcript_exon	Exon 12 of 14	ENSP00000420649.1

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

African (AFR) AF: 0.860 AC: 425 AN: 494

American (AMR) AF: 0.921 AC: 3262 AN: 3542

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 1433 AN: 1616

East Asian (EAS) AF: 0.981 AC: 1322 AN: 1348

South Asian (SAS) AF: 0.937 AC: 15611 AN: 16662

European-Finnish (FIN) AF: 0.875 AC: 3635 AN: 4154

Middle Eastern (MID) AF: 0.892 AC: 257 AN: 288

European-Non Finnish (NFE) AF: 0.879 AC: 43542 AN: 49528

Other (OTH) AF: 0.893 AC: 3635 AN: 4072

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

African (AFR) AF: 0.868 AC: 35996 AN: 41478

American (AMR) AF: 0.914 AC: 13984 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 3066 AN: 3472

East Asian (EAS) AF: 0.982 AC: 5083 AN: 5176

South Asian (SAS) AF: 0.949 AC: 4582 AN: 4828

European-Finnish (FIN) AF: 0.878 AC: 9303 AN: 10594

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.880 AC: 59856 AN: 68006

Other (OTH) AF: 0.886 AC: 1869 AN: 2110

Alfa AF: 0.888 Hom.: 30619

Bravo AF: 0.888

Asia WGS AF: 0.956 AC: 3326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.2
DANN	Benign	0.65
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6438759; hg19: chr3-122440066;