16-16908-C-T

Variant names:

• chr16-16908-C-T
• rs563301232

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000564273.4(WASH4P):​n.532+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,577,224 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (7 hom., cov: 30)
  • Exomes 𝑓: 0.0014 (7 hom.)
• Consequence: WASH4P ENST00000564273.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0640

Genes affected

WASH4P (HGNC:14126): (WASP family homolog 4, pseudogene) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in Arp2/3 complex-mediated actin nucleation and retrograde transport, endosome to Golgi. Predicted to be located in early endosome and recycling endosome. Predicted to be part of WASH complex. [provided by Alliance of Genome Resources, Apr 2022]

MIR6859-4 (HGNC:50840): (microRNA 6859-4) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-16908-C-T is Benign according to our data. Variant chr16-16908-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3770830.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WASH4P		n.16908C>T		intragenic_variant
MIR6859-4	NR_128720.1	n.*144G>A		downstream_gene_variant
MIR6859-4	unassigned_transcript_2760	n.*144G>A		downstream_gene_variant
MIR6859-4	unassigned_transcript_2761	n.*184G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WASH4P	ENST00000564273.4	n.532+8G>A		splice_region_variant, intron_variant	Intron 4 of 8	6
MIR6859-4	ENST00000615957.1	n.*144G>A		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 165 AN: 135564 Hom.: 7 Cov.: 30

Gnomad AFR AF: 0.000343

Gnomad AMI AF: 0.0117

Gnomad AMR AF: 0.000709

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000885

Gnomad FIN AF: 0.000202

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00200

Gnomad OTH AF: 0.000548

GnomAD3 exomes AF: 0.00133 AC: 282 AN: 212452 Hom.: 21 AF XY: 0.00149 AC XY: 172 AN XY: 115770

Gnomad AFR exome AF: 0.000303

Gnomad AMR exome AF: 0.000594

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00159

Gnomad FIN exome AF: 0.0000509

Gnomad NFE exome AF: 0.00225

Gnomad OTH exome AF: 0.00151

GnomAD4 exome AF: 0.00140 AC: 2015 AN: 1441568 Hom.: 7 Cov.: 55 AF XY: 0.00142 AC XY: 1019 AN XY: 717104

Gnomad4 AFR exome AF: 0.000220

Gnomad4 AMR exome AF: 0.000407

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00146

Gnomad4 FIN exome AF: 0.000115

Gnomad4 NFE exome AF: 0.00161

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.00122 AC: 165 AN: 135656 Hom.: 7 Cov.: 30 AF XY: 0.00109 AC XY: 72 AN XY: 66272

Gnomad4 AFR AF: 0.000342

Gnomad4 AMR AF: 0.000708

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000885

Gnomad4 FIN AF: 0.000202

Gnomad4 NFE AF: 0.00200

Gnomad4 OTH AF: 0.000541

Alfa AF: 0.00170 Hom.: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

WASH4P: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs563301232; hg19: chr16-66908;