chr1-111439982-T-A

Variant names:

• chr1-111439982-T-A
• rs3754032
• NM_024102.4:c.*1248A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ENSG00000243960 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024102.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR77	NM_024102.4	MANE Select	c.*1248A>T		3_prime_UTR	Exon 10 of 10	NP_077007.1
	WDR77	NR_133654.2		n.2222A>T		non_coding_transcript_exon	Exon 9 of 9
	WDR77	NM_001317062.2		c.*1248A>T		3_prime_UTR	Exon 10 of 10	NP_001303991.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR77	ENST00000235090.10	TSL:1 MANE Select	c.*1248A>T		3_prime_UTR	Exon 10 of 10	ENSP00000235090.5
	ENSG00000243960	ENST00000416099.1	TSL:2	n.537+710A>T		intron	N/A
	ENSG00000243960	ENST00000445680.1	TSL:3	n.227+1156A>T		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.304 AC: 129 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.0837 AC: 3474 AN: 41530

American (AMR) AF: 0.152 AC: 2325 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 506 AN: 3468

East Asian (EAS) AF: 0.130 AC: 673 AN: 5188

South Asian (SAS) AF: 0.236 AC: 1137 AN: 4822

European-Finnish (FIN) AF: 0.276 AC: 2917 AN: 10580

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18757 AN: 67986

Other (OTH) AF: 0.186 AC: 393 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.47
PhyloP100		-0.055
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: rs3754032; hg19: chr1-111982604;