rs6568634

chr6-110171485-A-Gchr6-110171485-A-T

Variant summary

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

The NM_003931.3(WASF1):c.-127+7113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,014 control chromosomes in the GnomAD database, including 4,338 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 0.20 (4338 hom., cov: 32)
• Consequence: WASF1 NM_003931.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

Genes affected

WASF1 (HGNC:12732): (WASP family member 1) The protein encoded by this gene, a member of the Wiskott-Aldrich syndrome protein (WASP)-family, plays a critical role downstream of Rac, a Rho-family small GTPase, in regulating the actin cytoskeleton required for membrane ruffling. It has been shown to associate with an actin nucleation core Arp2/3 complex while enhancing actin polymerization in vitro. Wiskott-Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WASF1	NM_003931.3	c.-127+7113T>C		intron_variant		ENST00000392589.6
WASF1	NM_001024934.2	c.-29+7113T>C		intron_variant
WASF1	NM_001024935.2	c.-127+7954T>C		intron_variant
WASF1	NM_001024936.2	c.-29+7954T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WASF1	ENST00000392589.6	c.-127+7113T>C		intron_variant		5	NM_003931.3	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30878 AN: 151894 Hom.: 4320 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.204 AC: 30953 AN: 152014 Hom.: 4338 Cov.: 32 AF XY: 0.204 AC XY: 15163 AN XY: 74330

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.175

Alfa AF: 0.144 Hom.: 972

Bravo AF: 0.218

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	2.3
Dann	Benign	0.24

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: rs6568634; hg19: chr6-110492688; COSMIC: COSV55618908;