rs3795443

Positions:

• chr1-225487301-A-G

Variant summary

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

The ENST00000366843.7(ENAH):​c.*10474T>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 0.134 in 152,250 control chromosomes in the GnomAD database, including 1,516 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 0.13 (1516 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENAH ENST00000366843.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENAH	NM_018212.6	c.*10474T>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.*10474T>C		3_prime_UTR_variant	14/14	1	NM_018212.6	ENSP00000355808	P2
ENAH	ENST00000366844.7	c.*10474T>C		3_prime_UTR_variant	15/15	1		ENSP00000355809	A2
ENAH	ENST00000696609.1	c.*10474T>C		3_prime_UTR_variant	12/12			ENSP00000512753

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20335 AN: 152132 Hom.: 1514 Cov.: 32

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.137

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.134 AC: 20362 AN: 152250 Hom.: 1516 Cov.: 32 AF XY: 0.137 AC XY: 10233 AN XY: 74446

Gnomad4 AFR AF: 0.0878

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.143

Alfa AF: 0.139 Hom.: 2157

Bravo AF: 0.127

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.074
DANN	Benign	0.38

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: rs3795443; hg19: chr1-225675003;