5-37436495-C-G

Variant summary

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

The NM_018034.4(WDR70):c.493-1427C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0337 in 152,186 control chromosomes in the GnomAD database, including 132 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 0.034 (132 hom., cov: 32)
• Consequence: WDR70 NM_018034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

Genes affected

WDR70 (HGNC:25495): (WD repeat domain 70) Enables enzyme binding activity. Predicted to be involved in regulation of DNA double-strand break processing and regulation of histone H2B conserved C-terminal lysine ubiquitination. Predicted to be active in nucleus and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR70	NM_018034.4	c.493-1427C>G		intron_variant		ENST00000265107.9
WDR70	NM_001345998.2	c.490-1427C>G		intron_variant
WDR70	NM_001345999.2	c.427-1427C>G		intron_variant
WDR70	XM_047417348.1	c.424-1427C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR70	ENST00000265107.9	c.493-1427C>G		intron_variant		1	NM_018034.4	P1
WDR70	ENST00000504564.1	c.493-1427C>G		intron_variant		1
WDR70	ENST00000511906.5	n.507-1427C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5108 AN: 152068 Hom.: 132 Cov.: 32

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0654

Gnomad FIN AF: 0.0570

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0297

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

GnomAD4 genome AF: 0.0337 AC: 5123 AN: 152186 Hom.: 132 Cov.: 32 AF XY: 0.0351 AC XY: 2611 AN XY: 74412

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.0713

Gnomad4 ASJ AF: 0.0398

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0661

Gnomad4 FIN AF: 0.0570

Gnomad4 NFE AF: 0.0325

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0327 Hom.: 6

Bravo AF: 0.0329

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	8.5
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs10491331; hg19: chr5-37436597;