rs9649465

Positions:

• chr7-123736506-G-A
• chr7-123736506-G-C
• chr7-123736506-G-T

Variant summary

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

The ENST00000223023.5(WASL):​c.117+12112C>T 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 151,908 control chromosomes in the GnomAD database, including 14,761 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 (14761 hom., cov: 32)
• Consequence: WASL ENST00000223023.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

Genes affected

WASL (HGNC:12735): (WASP like actin nucleation promoting factor) This gene encodes a member of the Wiskott-Aldrich syndrome (WAS) protein family. Wiskott-Aldrich syndrome proteins share similar domain structure, and associate with a variety of signaling molecules to alter the actin cytoskeleton. The encoded protein is highly expressed in neural tissues, and interacts with several proteins involved in cytoskeletal organization, including cell division control protein 42 (CDC42) and the actin-related protein-2/3 (ARP2/3) complex. The encoded protein may be involved in the formation of long actin microspikes, and in neurite extension. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASL	NM_003941.4	c.117+12112C>T		intron_variant		ENST00000223023.5	NP_003932.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASL	ENST00000223023.5	c.117+12112C>T		intron_variant		1	NM_003941.4	ENSP00000223023	P1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65716 AN: 151790 Hom.: 14768 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.433 AC: 65713 AN: 151908 Hom.: 14761 Cov.: 32 AF XY: 0.438 AC XY: 32522 AN XY: 74228

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.463

Alfa AF: 0.442 Hom.: 1851

Bravo AF: 0.422

Asia WGS AF: 0.578 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9649465; hg19: chr7-123376560;