1-225515783-A-G

Position:

• chr1-225515783-A-G

Variant summary

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

The NM_018212.6(ENAH):​c.914-883T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 151,942 control chromosomes in the GnomAD database, including 33,354 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 0.66 (33354 hom., cov: 31)
• Consequence: ENAH NM_018212.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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=-0.83).
• 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	Protein	UniProt
ENAH	NM_018212.6	c.914-883T>C		intron_variant		ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.914-883T>C		intron_variant		1	NM_018212.6	ENSP00000355808	P2
ENAH	ENST00000366844.7	c.914-883T>C		intron_variant		1		ENSP00000355809	A2
ENAH	ENST00000635051.1	c.1610-883T>C		intron_variant		5		ENSP00000489607	A2
ENAH	ENST00000696609.1	c.1232-883T>C		intron_variant				ENSP00000512753

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100154 AN: 151824 Hom.: 33362 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.659 AC: 100181 AN: 151942 Hom.: 33354 Cov.: 31 AF XY: 0.655 AC XY: 48680 AN XY: 74276

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.679

Alfa AF: 0.681 Hom.: 6534

Bravo AF: 0.662

Asia WGS AF: 0.570 AC: 1985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.7
DANN	Benign	0.66

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: rs10799319; hg19: chr1-225703485; COSMIC: COSV52866224; COSMIC: COSV52866224;