rs11842915

Positions:

• chr13-24436036-C-T

Variant summary

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

The NM_006437.4(PARP4):​c.3667-562G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 151,954 control chromosomes in the GnomAD database, including 2,116 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 0.16 (2116 hom., cov: 32)
• Consequence: PARP4 NM_006437.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248

Genes affected

PARP4 (HGNC:271): (poly(ADP-ribose) polymerase family member 4) This gene encodes poly(ADP-ribosyl)transferase-like 1 protein, which is capable of catalyzing a poly(ADP-ribosyl)ation reaction. This protein has a catalytic domain which is homologous to that of poly (ADP-ribosyl) transferase, but lacks an N-terminal DNA binding domain which activates the C-terminal catalytic domain of poly (ADP-ribosyl) transferase. Since this protein is not capable of binding DNA directly, its transferase activity may be activated by other factors such as protein-protein interaction mediated by the extensive carboxyl terminus. [provided by RefSeq, Jul 2008]

TPTE2P6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP4	NM_006437.4	c.3667-562G>A		intron_variant		ENST00000381989.4	NP_006428.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP4	ENST00000381989.4	c.3667-562G>A		intron_variant		1	NM_006437.4	ENSP00000371419.3
TPTE2P6	ENST00000445572.5	n.233+26732C>T		intron_variant		6

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24443 AN: 151840 Hom.: 2118 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0639

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.161 AC: 24434 AN: 151954 Hom.: 2116 Cov.: 32 AF XY: 0.154 AC XY: 11428 AN XY: 74276

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0635

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.185

Alfa AF: 0.172 Hom.: 3699

Bravo AF: 0.162

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.84

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: rs11842915; hg19: chr13-25010174; COSMIC: COSV67963834;