1-225528539-G-A

Variant names:

• chr1-225528539-G-A
• rs7555139
• NM_018212.6:c.434+2015C>T

Variant summary

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

The ENST00000366843.7(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 ENST00000366843.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000366843.7. 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.434+2015C>T		intron	N/A	NP_060682.2
	ENAH	NM_001420159.1		c.491+2015C>T		intron	N/A	NP_001407088.1
	ENAH	NM_001420160.1		c.434+2015C>T		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.434+2015C>T		intron	N/A	ENSP00000355808.2
	ENAH	ENST00000366844.7	TSL:1	c.434+2015C>T		intron	N/A	ENSP00000355809.2
	ENAH	ENST00000497899.6	TSL:1	c.284+2015C>T		intron	N/A	ENSP00000489106.1

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

African (AFR) AF: 0.628 AC: 26022 AN: 41434

American (AMR) AF: 0.671 AC: 10229 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2550 AN: 3464

East Asian (EAS) AF: 0.706 AC: 3634 AN: 5144

South Asian (SAS) AF: 0.442 AC: 2122 AN: 4802

European-Finnish (FIN) AF: 0.670 AC: 7069 AN: 10554

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48123 AN: 67940

Other (OTH) AF: 0.685 AC: 1449 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.7
DANN	Benign	0.63
PhyloP100		0.10
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: rs7555139; hg19: chr1-225716241; COSMIC: COSV52866241;