7-123684552-T-C

Variant names:

• chr7-123684552-T-C
• rs1015881630
• NM_003941.4:c.1485A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003941.4(WASL):​c.1485A>G​(p.Glu495Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000813 in 1,229,666 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: WASL NM_003941.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.48
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=3.48 with no splicing effect.

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.1485A>G	p.Glu495Glu	synonymous	Exon 11 of 11	NP_003932.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASL	ENST00000223023.5	TSL:1 MANE Select	c.1485A>G	p.Glu495Glu	synonymous	Exon 11 of 11	ENSP00000223023.4	O00401
	WASL	ENST00000924343.1		c.1479A>G	p.Glu493Glu	synonymous	Exon 11 of 11	ENSP00000594402.1
	WASL	ENST00000924344.1		c.1398A>G	p.Glu466Glu	synonymous	Exon 10 of 10	ENSP00000594403.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.13e-7 AC: 1 AN: 1229666 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 614002

African (AFR) AF: 0.00 AC: 0 AN: 27860

American (AMR) AF: 0.00 AC: 0 AN: 34380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23642

East Asian (EAS) AF: 0.00 AC: 0 AN: 34262

South Asian (SAS) AF: 0.00 AC: 0 AN: 73334

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5328

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 930650

Other (OTH) AF: 0.00 AC: 0 AN: 51886

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.5
DANN	Benign	0.55
PhyloP100		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8

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: rs1015881630; hg19: chr7-123324606;