rs3765689

Positions:

• chr1-3642918-A-G

Variant summary

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

The NM_017818.4(WRAP73):​c.339+3748T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 151,960 control chromosomes in the GnomAD database, including 319 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 0.044 (319 hom., cov: 31)
• Consequence: WRAP73 NM_017818.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831

Genes affected

WRAP73 (HGNC:12759): (WD repeat containing, antisense to TP73) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Studies of the related mouse protein suggest that the encoded protein may play a role in the process of ossification. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WRAP73	NM_017818.4	c.339+3748T>C		intron_variant		ENST00000270708.12	NP_060288.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WRAP73	ENST00000270708.12	c.339+3748T>C		intron_variant		1	NM_017818.4	ENSP00000270708.7

Frequencies

GnomAD3 genomes AF: 0.0442 AC: 6706 AN: 151842 Hom.: 320 Cov.: 31

Gnomad AFR AF: 0.00876

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0548

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0454

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0442 AC: 6710 AN: 151960 Hom.: 319 Cov.: 31 AF XY: 0.0457 AC XY: 3393 AN XY: 74254

Gnomad4 AFR AF: 0.00873

Gnomad4 AMR AF: 0.0548

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0473

Gnomad4 NFE AF: 0.0454

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0466 Hom.: 28

Bravo AF: 0.0443

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.37
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3765689; hg19: chr1-3559482;