chr3-167631050-G-A

Variant names:

• chr3-167631050-G-A
• rs7627289
• NM_001366157.1:c.166-3758C>T

Variant summary

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

The NM_001366157.1(WDR49):​c.166-3758C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,622 control chromosomes in the GnomAD database, including 2,825 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 0.19 (2825 hom., cov: 31)
• Consequence: WDR49 NM_001366157.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421
• Publications: 11 publications found

Genes affected

WDR49 (HGNC:26587): (WD repeat domain 49) This gene encodes a member of the WD repeat protein family with nine WD repeats. 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR49	NM_001366157.1	c.166-3758C>T		intron_variant	Intron 2 of 18	ENST00000682715.1	NP_001353086.1
WDR49	NM_001348951.2	c.166-3758C>T		intron_variant	Intron 2 of 18		NP_001335880.1
WDR49	NM_001348952.2	c.166-3758C>T		intron_variant	Intron 2 of 18		NP_001335881.1
WDR49	NM_001366158.1	c.-66+22211C>T		intron_variant	Intron 2 of 15		NP_001353087.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR49	ENST00000682715.1	c.166-3758C>T		intron_variant	Intron 2 of 18		NM_001366157.1	ENSP00000507497.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28058 AN: 151504 Hom.: 2820 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0532

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.185 AC: 28068 AN: 151622 Hom.: 2825 Cov.: 31 AF XY: 0.183 AC XY: 13549 AN XY: 74066

African (AFR) AF: 0.148 AC: 6104 AN: 41340

American (AMR) AF: 0.147 AC: 2236 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3468

East Asian (EAS) AF: 0.0532 AC: 272 AN: 5116

South Asian (SAS) AF: 0.226 AC: 1086 AN: 4810

European-Finnish (FIN) AF: 0.223 AC: 2346 AN: 10524

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.217 AC: 14759 AN: 67878

Other (OTH) AF: 0.159 AC: 336 AN: 2110

Alfa AF: 0.207 Hom.: 14285

Bravo AF: 0.178

Asia WGS AF: 0.156 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.42
DANN	Benign	0.52
PhyloP100		-0.42
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: rs7627289; hg19: chr3-167348838;