rs954534

chr1-225488628-T-C

Variant summary

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

The NM_018212.6(ENAH):c.*9147A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 152,242 control chromosomes in the GnomAD database, including 826 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 0.094 (826 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: 0.381

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENAH	NM_018212.6	c.*9147A>G		3_prime_UTR_variant	14/14	ENST00000366843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENAH	ENST00000366843.7	c.*9147A>G		3_prime_UTR_variant	14/14	1	NM_018212.6	P2
ENAH	ENST00000366844.7	c.*9147A>G		3_prime_UTR_variant	15/15	1		A2
ENAH	ENST00000696609.1	c.*9147A>G		3_prime_UTR_variant	12/12

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14265 AN: 152122 Hom.: 827 Cov.: 32

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.0845

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.0806

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0829

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

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.0937 AC: 14271 AN: 152240 Hom.: 826 Cov.: 32 AF XY: 0.0957 AC XY: 7127 AN XY: 74440

Gnomad4 AFR AF: 0.0485

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0660

Gnomad4 EAS AF: 0.0845

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.0806

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0820

Alfa AF: 0.106 Hom.: 915

Bravo AF: 0.0901

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.8
Dann	Benign	0.73

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: rs954534; hg19: chr1-225676330;