12-105155431-G-A

Position:

• chr12-105155431-G-A

Variant summary

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

The NM_015275.3(WASHC4):​c.2759-1295G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,832 control chromosomes in the GnomAD database, including 15,665 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 0.43 (15665 hom., cov: 31)
• Consequence: WASHC4 NM_015275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

Genes affected

WASHC4 (HGNC:29174): (WASH complex subunit 4) This gene encodes a component of the WASH complex, which functions in the intracellular transport of endosomes. Mutations in this gene have been detected in individuals with autosomal recessive cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC4	NM_015275.3	c.2759-1295G>A		intron_variant		ENST00000332180.10	NP_056090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASHC4	ENST00000332180.10	c.2759-1295G>A		intron_variant		1	NM_015275.3	ENSP00000328062	A1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65568 AN: 151714 Hom.: 15622 Cov.: 31

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.433 AC: 65679 AN: 151832 Hom.: 15665 Cov.: 31 AF XY: 0.426 AC XY: 31639 AN XY: 74196

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.386

Alfa AF: 0.384 Hom.: 5810

Bravo AF: 0.444

Asia WGS AF: 0.325 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.64

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: rs1663563; hg19: chr12-105549209;