rs7651446

Variant names:

• chr3-156689208-G-T
• rs7651446
• NM_015508.5:c.918-4812G>T

Variant summary

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

The NM_015508.5(TIPARP):​c.918-4812G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 152,100 control chromosomes in the GnomAD database, including 660 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 0.075 (660 hom., cov: 32)
• Consequence: TIPARP NM_015508.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453
• Publications: 28 publications found

Genes affected

TIPARP (HGNC:23696): (TCDD inducible poly(ADP-ribose) polymerase) This gene encodes a member of the poly(ADP-ribose) polymerase superfamily. Studies of the mouse ortholog have shown that the encoded protein catalyzes histone poly(ADP-ribosyl)ation and may be involved in T-cell function. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

TIPARP-AS1 (HGNC:41028): (TIPARP antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIPARP	NM_015508.5	c.918-4812G>T		intron_variant	Intron 2 of 5	ENST00000295924.12	NP_056323.2
TIPARP	NM_001184717.1	c.918-4812G>T		intron_variant	Intron 2 of 5		NP_001171646.1
TIPARP	NM_001184718.2	c.918-4812G>T		intron_variant	Intron 2 of 5		NP_001171647.1
TIPARP	XM_047447935.1	c.918-4812G>T		intron_variant	Intron 2 of 5		XP_047303891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIPARP	ENST00000295924.12	c.918-4812G>T		intron_variant	Intron 2 of 5	1	NM_015508.5	ENSP00000295924.7

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11422 AN: 151982 Hom.: 657 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00664

Gnomad FIN AF: 0.0728

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0441

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

GnomAD4 genome AF: 0.0752 AC: 11435 AN: 152100 Hom.: 660 Cov.: 32 AF XY: 0.0739 AC XY: 5494 AN XY: 74378

African (AFR) AF: 0.160 AC: 6631 AN: 41458

American (AMR) AF: 0.0328 AC: 502 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0300 AC: 104 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.00664 AC: 32 AN: 4816

European-Finnish (FIN) AF: 0.0728 AC: 771 AN: 10590

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0483 AC: 3285 AN: 67980

Other (OTH) AF: 0.0436 AC: 92 AN: 2110

Alfa AF: 0.0586 Hom.: 777

Bravo AF: 0.0774

Asia WGS AF: 0.0160 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.53
PhyloP100		0.45
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: rs7651446; hg19: chr3-156406997;