12-105116557-A-G

Position:

• chr12-105116557-A-G

Variant summary

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

The NM_015275.3(WASHC4):​c.435+829A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,138 control chromosomes in the GnomAD database, including 59,004 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 0.88 (59004 hom., cov: 31)
• Consequence: WASHC4 NM_015275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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]

WASHC4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASHC4	NM_015275.3	c.435+829A>G		intron_variant		ENST00000332180.10	NP_056090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASHC4	ENST00000332180.10	c.435+829A>G		intron_variant		1	NM_015275.3	ENSP00000328062.6

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133545 AN: 152020 Hom.: 58946 Cov.: 31

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.920

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.879 AC: 133661 AN: 152138 Hom.: 59004 Cov.: 31 AF XY: 0.884 AC XY: 65755 AN XY: 74356

Gnomad4 AFR AF: 0.935

Gnomad4 AMR AF: 0.902

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.948

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.875

Alfa AF: 0.851 Hom.: 6882

Bravo AF: 0.881

Asia WGS AF: 0.964 AC: 3352 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.3
DANN	Benign	0.68

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: rs1196800; hg19: chr12-105510335;