rs12034829

Positions:

• chr1-225516585-C-A
• chr1-225516585-C-G
• chr1-225516585-C-T

Variant summary

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

The NM_018212.6(ENAH):​c.913+611G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,172 control chromosomes in the GnomAD database, including 53,324 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 0.84 (53324 hom., cov: 32)
• Consequence: ENAH NM_018212.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENAH	NM_018212.6	c.913+611G>T		intron_variant		ENST00000366843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENAH	ENST00000366843.7	c.913+611G>T		intron_variant		1	NM_018212.6	P2
ENAH	ENST00000366844.7	c.913+611G>T		intron_variant		1		A2
ENAH	ENST00000635051.1	c.1609+611G>T		intron_variant		5		A2
ENAH	ENST00000696609.1	c.1231+611G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127171 AN: 152054 Hom.: 53283 Cov.: 32

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.836 AC: 127269 AN: 152172 Hom.: 53324 Cov.: 32 AF XY: 0.835 AC XY: 62131 AN XY: 74412

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.848

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.847

Gnomad4 OTH AF: 0.858

Alfa AF: 0.833 Hom.: 23688

Bravo AF: 0.837

Asia WGS AF: 0.779 AC: 2710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.47

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: rs12034829; hg19: chr1-225704287; COSMIC: COSV52866229; COSMIC: COSV52866229;