1-225556635-C-T

Variant names:

• chr1-225556635-C-T
• rs576861
• NM_018212.6:c.172-1552G>A

Variant summary

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

The NM_018212.6(ENAH):​c.172-1552G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 151,912 control chromosomes in the GnomAD database, including 33,396 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 0.66 (33396 hom., cov: 31)
• Consequence: ENAH NM_018212.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAH	NM_018212.6	c.172-1552G>A		intron_variant	Intron 2 of 13	ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.172-1552G>A		intron_variant	Intron 2 of 13	1	NM_018212.6	ENSP00000355808.2

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100212 AN: 151794 Hom.: 33403 Cov.: 31

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.686

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.660 AC: 100241 AN: 151912 Hom.: 33396 Cov.: 31 AF XY: 0.656 AC XY: 48696 AN XY: 74262

African (AFR) AF: 0.586 AC: 24261 AN: 41404

American (AMR) AF: 0.662 AC: 10107 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2553 AN: 3470

East Asian (EAS) AF: 0.709 AC: 3659 AN: 5162

South Asian (SAS) AF: 0.442 AC: 2126 AN: 4808

European-Finnish (FIN) AF: 0.671 AC: 7069 AN: 10534

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48115 AN: 67954

Other (OTH) AF: 0.679 AC: 1432 AN: 2108

Alfa AF: 0.679 Hom.: 17839

Bravo AF: 0.662

Asia WGS AF: 0.566 AC: 1973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.33
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: rs576861; hg19: chr1-225744337; COSMIC: COSV52866279;