rs10915846

Positions:

• chr1-225523485-G-A
• chr1-225523485-G-C
• chr1-225523485-G-T

Variant summary

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

The NM_018212.6(ENAH):​c.435-3920C>T 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 151,868 control chromosomes in the GnomAD database, including 3,931 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 (3931 hom., cov: 31)
• Consequence: ENAH NM_018212.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

Genes affected

ENAH (HGNC:18271): (ENAH actin regulator) This gene encodes a member of the enabled/ vasodilator-stimulated phosphoprotein. Members of this gene family are involved in actin-based motility. This protein is involved in regulating the assembly of actin filaments and modulates cell adhesion and motility. Alternate splice variants of this gene have been correlated with tumor invasiveness in certain tissues and these variants may serve as prognostic markers. A pseudogene of this gene is found on chromosome 3. [provided by RefSeq, Sep 2016]

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 (AMR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENAH	NM_018212.6	c.435-3920C>T		intron_variant		ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.435-3920C>T		intron_variant		1	NM_018212.6	ENSP00000355808	P2

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30993 AN: 151750 Hom.: 3931 Cov.: 31

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.204 AC: 30986 AN: 151868 Hom.: 3931 Cov.: 31 AF XY: 0.201 AC XY: 14877 AN XY: 74170

Gnomad4 AFR AF: 0.0514

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.236

Alfa AF: 0.227 Hom.: 2012

Bravo AF: 0.207

Asia WGS AF: 0.117 AC: 405 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.34

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: rs10915846; hg19: chr1-225711187;