chr1-225492540-A-G

Position:

• chr1-225492540-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.*5235T>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 0.086 in 152,062 control chromosomes in the GnomAD database, including 772 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 0.086 (772 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENAH NM_018212.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENAH	NM_018212.6	c.*5235T>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	c.*5235T>C		3_prime_UTR_variant	14/14	1	NM_018212.6	ENSP00000355808.2
ENAH	ENST00000366844	c.*5235T>C		3_prime_UTR_variant	15/15	1		ENSP00000355809.2
ENAH	ENST00000696609	c.*5235T>C		3_prime_UTR_variant	12/12			ENSP00000512753.1

Frequencies

GnomAD3 genomes AF: 0.0860 AC: 13070 AN: 151944 Hom.: 773 Cov.: 31

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.0843

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0798

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0860 AC: 13072 AN: 152062 Hom.: 772 Cov.: 31 AF XY: 0.0877 AC XY: 6522 AN XY: 74326

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0640

Gnomad4 EAS AF: 0.0843

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.0808

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0789

Alfa AF: 0.0989 Hom.: 170

Bravo AF: 0.0817

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.45

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: rs1764345; hg19: chr1-225680242;