rs12043633

Variant names:

• chr1-225488869-G-A
• rs12043633
• NM_018212.6:c.*8906C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018212.6(ENAH):​c.*8906C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,204 control chromosomes in the GnomAD database, including 1,853 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 (1853 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: ENAH NM_018212.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAH	NM_018212.6	c.*8906C>T		3_prime_UTR_variant	Exon 14 of 14	ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.*8906C>T		3_prime_UTR_variant	Exon 14 of 14	1	NM_018212.6	ENSP00000355808.2
ENAH	ENST00000366844.7	c.*8906C>T		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000355809.2
ENAH	ENST00000696609.1	c.*8906C>T		3_prime_UTR_variant	Exon 12 of 12			ENSP00000512753.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20140 AN: 152080 Hom.: 1856 Cov.: 32

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.132 AC: 20129 AN: 152198 Hom.: 1853 Cov.: 32 AF XY: 0.136 AC XY: 10144 AN XY: 74404

African (AFR) AF: 0.0314 AC: 1304 AN: 41538

American (AMR) AF: 0.142 AC: 2173 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0651 AC: 226 AN: 3470

East Asian (EAS) AF: 0.383 AC: 1978 AN: 5168

South Asian (SAS) AF: 0.133 AC: 642 AN: 4820

European-Finnish (FIN) AF: 0.214 AC: 2260 AN: 10576

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11045 AN: 68008

Other (OTH) AF: 0.131 AC: 278 AN: 2116

Alfa AF: 0.140 Hom.: 1073

Bravo AF: 0.126

Asia WGS AF: 0.222 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.62
DANN	Benign	0.52
PhyloP100		0.057
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12043633; hg19: chr1-225676571;