rs487591

Variant names:

• chr1-225569049-T-C
• rs487591
• NM_018212.6:c.6-1635A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001420159.1(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_001420159.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001420159.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENAH	NM_018212.6	MANE Select	c.6-1635A>G		intron	N/A	NP_060682.2
	ENAH	NM_001420159.1		c.6-1635A>G		intron	N/A	NP_001407088.1
	ENAH	NM_001420160.1		c.6-1635A>G		intron	N/A	NP_001407089.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENAH	ENST00000366843.7	TSL:1 MANE Select	c.6-1635A>G		intron	N/A	ENSP00000355808.2
	ENAH	ENST00000366844.7	TSL:1	c.6-1635A>G		intron	N/A	ENSP00000355809.2
	ENAH	ENST00000893225.1		c.6-1635A>G		intron	N/A	ENSP00000563284.1

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

African (AFR) AF: 0.823 AC: 34141 AN: 41492

American (AMR) AF: 0.694 AC: 10607 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2554 AN: 3472

East Asian (EAS) AF: 0.710 AC: 3678 AN: 5182

South Asian (SAS) AF: 0.464 AC: 2240 AN: 4824

European-Finnish (FIN) AF: 0.673 AC: 7118 AN: 10570

Middle Eastern (MID) AF: 0.774 AC: 226 AN: 292

European-Non Finnish (NFE) AF: 0.709 AC: 48216 AN: 67994

Other (OTH) AF: 0.731 AC: 1540 AN: 2108

Alfa AF: 0.719 Hom.: 48738

Bravo AF: 0.742

Asia WGS AF: 0.590 AC: 2051 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs487591; hg19: chr1-225756751;