1-225487757-A-G

Position:

• chr1-225487757-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.*10018T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,050 control chromosomes in the GnomAD database, including 33,519 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 (33519 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: ENAH NM_018212.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524

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 (EAS) 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.*10018T>C		3_prime_UTR_variant	14/14	ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.*10018T>C		3_prime_UTR_variant	14/14	1	NM_018212.6	ENSP00000355808	P2
ENAH	ENST00000366844.7	c.*10018T>C		3_prime_UTR_variant	15/15	1		ENSP00000355809	A2
ENAH	ENST00000696609.1	c.*10018T>C		3_prime_UTR_variant	12/12			ENSP00000512753

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100439 AN: 151930 Hom.: 33526 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.686

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.661 AC: 100470 AN: 152048 Hom.: 33519 Cov.: 32 AF XY: 0.656 AC XY: 48792 AN XY: 74338

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.680

Alfa AF: 0.695 Hom.: 50113

Bravo AF: 0.664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.74

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: rs4653643; hg19: chr1-225675459; COSMIC: COSV64772980;