rs7627289

Positions:

• chr3-167631050-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
WDR49	NM_001366157.1	c.166-3758C>T		intron_variant		ENST00000682715.1
WDR49	NM_001348951.2	c.166-3758C>T		intron_variant
WDR49	NM_001348952.2	c.166-3758C>T		intron_variant
WDR49	NM_001366158.1	c.-66+22211C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR49	ENST00000682715.1	c.166-3758C>T		intron_variant			NM_001366157.1	A2

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

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.0532

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.159

Alfa AF: 0.211 Hom.: 6955

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7627289; hg19: chr3-167348838;