6-110171485-A-G

Variant names:

• chr6-110171485-A-G
• rs6568634
• NM_003931.3:c.-127+7113T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

WASF1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with absent language and variable seizures

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003931.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASF1	NM_003931.3	MANE Select	c.-127+7113T>C		intron	N/A	NP_003922.1
	WASF1	NM_001024934.2		c.-29+7113T>C		intron	N/A	NP_001020105.1
	WASF1	NM_001024935.2		c.-127+7954T>C		intron	N/A	NP_001020106.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASF1	ENST00000392589.6	TSL:5 MANE Select	c.-127+7113T>C		intron	N/A	ENSP00000376368.1
	WASF1	ENST00000359451.6	TSL:1	c.-127+7954T>C		intron	N/A	ENSP00000352425.2
	WASF1	ENST00000392587.6	TSL:1	c.-29+7954T>C		intron	N/A	ENSP00000376366.2

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

African (AFR) AF: 0.398 AC: 16465 AN: 41400

American (AMR) AF: 0.171 AC: 2617 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1137 AN: 5160

South Asian (SAS) AF: 0.245 AC: 1181 AN: 4824

European-Finnish (FIN) AF: 0.102 AC: 1082 AN: 10596

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7468 AN: 67974

Other (OTH) AF: 0.175 AC: 369 AN: 2114

Alfa AF: 0.177 Hom.: 2084

Bravo AF: 0.218

Asia WGS AF: 0.238 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.3
DANN	Benign	0.24
PhyloP100		-1.1
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: rs6568634; hg19: chr6-110492688; COSMIC: COSV55618908;