rs202224715

Variant names:

• chr2-238100477-C-A
• rs202224715
• NM_194312.4:c.58C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-238100477-C-A
• chr2-238100477-C-T

Variant summary

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

The NM_194312.4(ESPNL):​c.58C>A​(p.Arg20Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,208 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ESPNL NM_194312.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 0 publications found

Genes affected

ESPNL (HGNC:27937): (espin like) Predicted to enable actin filament binding activity. Predicted to be involved in actin filament bundle assembly and sensory perception of sound. Predicted to be located in stereocilium tip. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.57).
• BP7: Synonymous conserved (PhyloP=1.07 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194312.4. 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
	ESPNL	NM_194312.4	MANE Select	c.58C>A	p.Arg20Arg	synonymous	Exon 1 of 9	NP_919288.2	Q6ZVH7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESPNL	ENST00000343063.8	TSL:2 MANE Select	c.58C>A	p.Arg20Arg	synonymous	Exon 1 of 9	ENSP00000339115.3	Q6ZVH7-1
	ESPNL	ENST00000409169.5	TSL:5	c.58C>A	p.Arg20Arg	synonymous	Exon 1 of 8	ENSP00000386577.1	Q6ZVH7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451208 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721204

African (AFR) AF: 0.00 AC: 0 AN: 33228

American (AMR) AF: 0.00 AC: 0 AN: 43384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25736

East Asian (EAS) AF: 0.00 AC: 0 AN: 39228

South Asian (SAS) AF: 0.00 AC: 0 AN: 84414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109300

Other (OTH) AF: 0.00 AC: 0 AN: 59956

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.2
DANN	Benign	0.74
PhyloP100		1.1
PromoterAI		-0.0052	Neutral
Mutation Taster		=100/0	polymorphism

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: rs202224715; hg19: chr2-239009118;