chr5-37691146-A-T

Variant names:

• chr5-37691146-A-T
• rs12519943
• NM_018034.4:c.1093-6509A>T

Variant summary

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

The NM_018034.4(WDR70):​c.1093-6509A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,126 control chromosomes in the GnomAD database, including 5,102 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 0.24 (5102 hom., cov: 33)
• Consequence: WDR70 NM_018034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832
• Publications: 1 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018034.4. 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
	WDR70	NM_018034.4	MANE Select	c.1093-6509A>T		intron	N/A	NP_060504.1
	WDR70	NM_001345998.2		c.1090-6509A>T		intron	N/A	NP_001332927.1
	WDR70	NM_001345999.2		c.1027-6509A>T		intron	N/A	NP_001332928.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR70	ENST00000265107.9	TSL:1 MANE Select	c.1093-6509A>T		intron	N/A	ENSP00000265107.4
	WDR70	ENST00000504564.1	TSL:1	c.*26+3139A>T		intron	N/A	ENSP00000425841.1
	WDR70	ENST00000510699.1	TSL:5	n.450-6509A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36712 AN: 152008 Hom.: 5095 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.241 AC: 36720 AN: 152126 Hom.: 5102 Cov.: 33 AF XY: 0.246 AC XY: 18264 AN XY: 74368

African (AFR) AF: 0.113 AC: 4708 AN: 41518

American (AMR) AF: 0.378 AC: 5781 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1843 AN: 5176

South Asian (SAS) AF: 0.323 AC: 1560 AN: 4824

European-Finnish (FIN) AF: 0.275 AC: 2900 AN: 10562

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18247 AN: 67974

Other (OTH) AF: 0.230 AC: 487 AN: 2116

Alfa AF: 0.245 Hom.: 577

Bravo AF: 0.245

Asia WGS AF: 0.336 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.44
DANN	Benign	0.12
PhyloP100		-0.83
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: rs12519943; hg19: chr5-37691248;