rs7555139

chr1-225528539-G-Achr1-225528539-G-C

Variant summary

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

The NM_018212.6(ENAH):c.434+2015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 151,896 control chromosomes in the GnomAD database, including 34,576 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 0.67 (34576 hom., cov: 30)
• Consequence: ENAH NM_018212.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENAH	NM_018212.6	c.434+2015C>T		intron_variant		ENST00000366843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENAH	ENST00000366843.7	c.434+2015C>T		intron_variant		1	NM_018212.6	P2

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102082 AN: 151776 Hom.: 34581 Cov.: 30

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.672 AC: 102117 AN: 151896 Hom.: 34576 Cov.: 30 AF XY: 0.668 AC XY: 49569 AN XY: 74234

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.685

Alfa AF: 0.690 Hom.: 6910

Bravo AF: 0.677

Asia WGS AF: 0.571 AC: 1990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	2.7
Dann	Benign	0.63

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: rs7555139; hg19: chr1-225716241; COSMIC: COSV52866241;