1-225494473-C-T

Position:

• chr1-225494473-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.*3302G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,144 control chromosomes in the GnomAD database, including 53,513 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 0.84 (53513 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: ENAH NM_018212.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENAH	NM_018212.6	c.*3302G>A		3_prime_UTR_variant	14/14	ENST00000366843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENAH	ENST00000366843.7	c.*3302G>A		3_prime_UTR_variant	14/14	1	NM_018212.6	P2
ENAH	ENST00000366844.7	c.*3302G>A		3_prime_UTR_variant	15/15	1		A2
ENAH	ENST00000696609.1	c.*3302G>A		3_prime_UTR_variant	12/12

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127393 AN: 152026 Hom.: 53471 Cov.: 31

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.859

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.838 AC: 127492 AN: 152144 Hom.: 53513 Cov.: 31 AF XY: 0.836 AC XY: 62225 AN XY: 74390

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.850

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.847

Gnomad4 OTH AF: 0.860

Alfa AF: 0.842 Hom.: 15492

Bravo AF: 0.839

Asia WGS AF: 0.778 AC: 2703 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.75
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: rs2039620; hg19: chr1-225682175; COSMIC: COSV52866208; COSMIC: COSV52866208;