chr7-123736506-G-A

Variant names:

• chr7-123736506-G-A
• rs9649465
• NM_003941.4:c.117+12112C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003941.4(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 NM_003941.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003941.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASL	NM_003941.4	MANE Select	c.117+12112C>T		intron	N/A	NP_003932.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASL	ENST00000223023.5	TSL:1 MANE Select	c.117+12112C>T		intron	N/A	ENSP00000223023.4	O00401
	WASL	ENST00000924343.1		c.117+12112C>T		intron	N/A	ENSP00000594402.1
	WASL	ENST00000924344.1		c.117+12112C>T		intron	N/A	ENSP00000594403.1

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

African (AFR) AF: 0.314 AC: 13022 AN: 41412

American (AMR) AF: 0.455 AC: 6956 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1763 AN: 3470

East Asian (EAS) AF: 0.548 AC: 2832 AN: 5168

South Asian (SAS) AF: 0.664 AC: 3205 AN: 4826

European-Finnish (FIN) AF: 0.477 AC: 5025 AN: 10540

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.460 AC: 31260 AN: 67910

Other (OTH) AF: 0.463 AC: 977 AN: 2110

Alfa AF: 0.437 Hom.: 1894

Bravo AF: 0.422

Asia WGS AF: 0.578 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.73
PhyloP100		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs9649465; hg19: chr7-123376560;