rs1075364

Positions:

• chr1-225627933-C-T

Variant summary

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

The NM_018212.6(ENAH):​c.5+24753G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 147,100 control chromosomes in the GnomAD database, including 29,583 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 0.64 (29583 hom., cov: 31)
• Consequence: ENAH NM_018212.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENAH	NM_018212.6	c.5+24753G>A		intron_variant		ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.5+24753G>A		intron_variant		1	NM_018212.6	ENSP00000355808	P2
ENAH	ENST00000366844.7	c.5+24753G>A		intron_variant		1		ENSP00000355809	A2
ENAH	ENST00000284563.7	c.5+24753G>A		intron_variant		5		ENSP00000284563
ENAH	ENST00000635051.1	c.5+24753G>A		intron_variant		5		ENSP00000489607	A2

Frequencies

GnomAD3 genomes AF: 0.641 AC: 94206 AN: 146992 Hom.: 29549 Cov.: 31

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.470

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.641 AC: 94291 AN: 147100 Hom.: 29583 Cov.: 31 AF XY: 0.644 AC XY: 46187 AN XY: 71770

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.627

Alfa AF: 0.605 Hom.: 22001

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.1
DANN	Benign	0.42

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: rs1075364; hg19: chr1-225815635; COSMIC: COSV52866372;