rs487591

Positions:

• chr1-225569049-T-C

Variant summary

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

The NM_018212.6(ENAH):​c.6-1635A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,134 control chromosomes in the GnomAD database, including 40,864 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 0.73 (40864 hom., cov: 32)
• Consequence: ENAH NM_018212.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

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 (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENAH	NM_018212.6	c.6-1635A>G		intron_variant		ENST00000366843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENAH	ENST00000366843.7	c.6-1635A>G		intron_variant		1	NM_018212.6	P2

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110951 AN: 152016 Hom.: 40846 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.736

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

GnomAD4 genome AF: 0.730 AC: 111024 AN: 152134 Hom.: 40864 Cov.: 32 AF XY: 0.724 AC XY: 53852 AN XY: 74360

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.731

Alfa AF: 0.716 Hom.: 36758

Bravo AF: 0.742

Asia WGS AF: 0.590 AC: 2051 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.67

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: rs487591; hg19: chr1-225756751;