chr1-111439982-T-A

Position:

• chr1-111439982-T-A

Variant summary

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

The NM_024102.4(WDR77):​c.*1248A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,616 control chromosomes in the GnomAD database, including 3,701 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 0.20 (3684 hom., cov: 32)
  • Exomes 𝑓: 0.30 (17 hom.)
• Consequence: WDR77 NM_024102.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550

Genes affected

WDR77 (HGNC:29652): (WD repeat domain 77) The protein encoded by this gene is an androgen receptor coactivator that forms a complex with protein arginine methyltransferase 5, which modifies specific arginines to dimethylarginines in several spliceosomal Sm proteins. The encoded protein may be involved in the early stages of prostate cancer, with most of the protein being nuclear-localized in benign cells but cytoplasmic in cancer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

WDR77 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR77	NM_024102.4	c.*1248A>T		3_prime_UTR_variant	10/10	ENST00000235090.10	NP_077007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR77	ENST00000235090	c.*1248A>T		3_prime_UTR_variant	10/10	1	NM_024102.4	ENSP00000235090.5
ENSG00000243960	ENST00000416099.1	n.537+710A>T		intron_variant		2
ENSG00000243960	ENST00000445680.1	n.227+1156A>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30500 AN: 152066 Hom.: 3684 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.301 AC: 130 AN: 432 Hom.: 17 Cov.: 0 AF XY: 0.286 AC XY: 75 AN XY: 262

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.200 AC: 30502 AN: 152184 Hom.: 3684 Cov.: 32 AF XY: 0.202 AC XY: 15023 AN XY: 74414

Gnomad4 AFR AF: 0.0837

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.186

Alfa AF: 0.153 Hom.: 340

Bravo AF: 0.181

Asia WGS AF: 0.166 AC: 579 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.47

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: rs3754032; hg19: chr1-111982604;