chr1-225487301-A-G

Variant names:

• chr1-225487301-A-G
• rs3795443
• NM_018212.6:c.*10474T>C

Variant summary

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

The NM_018212.6(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 NM_018212.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90
• Publications: 6 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=-0.87).
• 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 rank	MANE	Protein	UniProt
ENAH	NM_018212.6	c.*10474T>C		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.*10474T>C		3_prime_UTR_variant	Exon 14 of 14	1	NM_018212.6	ENSP00000355808.2
ENAH	ENST00000366844.7	c.*10474T>C		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000355809.2
ENAH	ENST00000696609.1	c.*10474T>C		3_prime_UTR_variant	Exon 12 of 12			ENSP00000512753.1

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

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) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0878 AC: 3647 AN: 41546

American (AMR) AF: 0.169 AC: 2581 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3472

East Asian (EAS) AF: 0.119 AC: 615 AN: 5186

South Asian (SAS) AF: 0.209 AC: 1007 AN: 4822

European-Finnish (FIN) AF: 0.212 AC: 2242 AN: 10596

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9313 AN: 68014

Other (OTH) AF: 0.143 AC: 302 AN: 2116

Alfa AF: 0.138 Hom.: 2657

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
PhyloP100		-2.9
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: rs3795443; hg19: chr1-225675003;