1-3638864-G-T

Variant names:

• chr1-3638864-G-T
• rs3818330
• NM_017818.4:c.340-42C>A

Variant summary

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

The NM_017818.4(WRAP73):​c.340-42C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,607,550 control chromosomes in the GnomAD database, including 40,176 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 0.18 (2910 hom., cov: 33)
  • Exomes 𝑓: 0.22 (37266 hom.)
• Consequence: WRAP73 NM_017818.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 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.340-42C>A		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.340-42C>A		intron	N/A	ENSP00000270708.7	Q9P2S5
	WRAP73	ENST00000378322.7	TSL:1	c.340-42C>A		intron	N/A	ENSP00000367573.3	A0A0A0MRV3
	WRAP73	ENST00000471223.1	TSL:1	n.762C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27134 AN: 152076 Hom.: 2906 Cov.: 33

Gnomad AFR AF: 0.0589

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.191

GnomAD2 exomes AF: 0.221 AC: 55390 AN: 250556 AF XY: 0.227

Gnomad AFR exome AF: 0.0545

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.355

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.215

Gnomad OTH exome AF: 0.212

GnomAD4 exome AF: 0.222 AC: 322534 AN: 1455356 Hom.: 37266 Cov.: 29 AF XY: 0.223 AC XY: 161713 AN XY: 724188

African (AFR) AF: 0.0501 AC: 1672 AN: 33368

American (AMR) AF: 0.185 AC: 8241 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 4989 AN: 26074

East Asian (EAS) AF: 0.335 AC: 13275 AN: 39634

South Asian (SAS) AF: 0.265 AC: 22846 AN: 86104

European-Finnish (FIN) AF: 0.267 AC: 14208 AN: 53238

Middle Eastern (MID) AF: 0.190 AC: 1095 AN: 5754

European-Non Finnish (NFE) AF: 0.220 AC: 243352 AN: 1106376

Other (OTH) AF: 0.214 AC: 12856 AN: 60178

GnomAD4 genome AF: 0.178 AC: 27142 AN: 152194 Hom.: 2910 Cov.: 33 AF XY: 0.184 AC XY: 13657 AN XY: 74410

African (AFR) AF: 0.0589 AC: 2446 AN: 41554

American (AMR) AF: 0.201 AC: 3081 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 685 AN: 3472

East Asian (EAS) AF: 0.341 AC: 1758 AN: 5160

South Asian (SAS) AF: 0.265 AC: 1276 AN: 4822

European-Finnish (FIN) AF: 0.275 AC: 2909 AN: 10588

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14221 AN: 67990

Other (OTH) AF: 0.190 AC: 401 AN: 2110

Alfa AF: 0.186 Hom.: 975

Bravo AF: 0.170

Asia WGS AF: 0.274 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.55
PhyloP100		0.0080
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: rs3818330; hg19: chr1-3555428; COSMIC: COSV54561930; COSMIC: COSV54561930;