12-105116557-A-G

Variant names:

• chr12-105116557-A-G
• rs1196800
• NM_015275.3:c.435+829A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal recessive 43

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
WASHC4	NM_015275.3	c.435+829A>G		intron_variant	Intron 6 of 32	ENST00000332180.10	NP_056090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WASHC4	ENST00000332180.10	c.435+829A>G		intron_variant	Intron 6 of 32	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

African (AFR) AF: 0.935 AC: 38834 AN: 41524

American (AMR) AF: 0.902 AC: 13781 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3137 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5162 AN: 5168

South Asian (SAS) AF: 0.948 AC: 4570 AN: 4820

European-Finnish (FIN) AF: 0.893 AC: 9458 AN: 10594

Middle Eastern (MID) AF: 0.921 AC: 269 AN: 292

European-Non Finnish (NFE) AF: 0.821 AC: 55839 AN: 67976

Other (OTH) AF: 0.875 AC: 1849 AN: 2112

Alfa AF: 0.854 Hom.: 7213

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
PhyloP100		-0.21
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: rs1196800; hg19: chr12-105510335;