rs3765689

Variant names:

• chr1-3642918-A-G
• rs3765689
• NM_017818.4:c.339+3748T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017818.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WRAP73	NM_017818.4	MANE Select	c.339+3748T>C		intron	N/A	NP_060288.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WRAP73	ENST00000270708.12	TSL:1 MANE Select	c.339+3748T>C		intron	N/A	ENSP00000270708.7	Q9P2S5
	WRAP73	ENST00000378322.7	TSL:1	c.339+3748T>C		intron	N/A	ENSP00000367573.3	A0A0A0MRV3
	WRAP73	ENST00000960493.1		c.339+3748T>C		intron	N/A	ENSP00000630552.1

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

African (AFR) AF: 0.00873 AC: 362 AN: 41466

American (AMR) AF: 0.0548 AC: 837 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0297 AC: 103 AN: 3468

East Asian (EAS) AF: 0.225 AC: 1152 AN: 5128

South Asian (SAS) AF: 0.106 AC: 510 AN: 4796

European-Finnish (FIN) AF: 0.0473 AC: 500 AN: 10560

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0454 AC: 3085 AN: 67960

Other (OTH) AF: 0.0421 AC: 89 AN: 2112

Alfa AF: 0.0523 Hom.: 397

Bravo AF: 0.0443

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.37
DANN	Benign	0.42
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3765689; hg19: chr1-3559482;