chr1-225515783-A-G

Variant names:

• chr1-225515783-A-G
• rs10799319
• NM_018212.6:c.914-883T>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.914-883T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 151,942 control chromosomes in the GnomAD database, including 33,354 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 (33354 hom., cov: 31)
• Consequence: ENAH NM_018212.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) 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.914-883T>C		intron_variant	Intron 6 of 13	ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.914-883T>C		intron_variant	Intron 6 of 13	1	NM_018212.6	ENSP00000355808.2
ENAH	ENST00000366844.7	c.914-883T>C		intron_variant	Intron 6 of 14	1		ENSP00000355809.2
ENAH	ENST00000635051.1	c.1610-883T>C		intron_variant	Intron 7 of 14	5		ENSP00000489607.1
ENAH	ENST00000696609.1	c.1232-883T>C		intron_variant	Intron 3 of 11			ENSP00000512753.1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100154 AN: 151824 Hom.: 33362 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.755

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: 0.659 AC: 100181 AN: 151942 Hom.: 33354 Cov.: 31 AF XY: 0.655 AC XY: 48680 AN XY: 74276

African (AFR) AF: 0.581 AC: 24086 AN: 41424

American (AMR) AF: 0.665 AC: 10154 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2547 AN: 3462

East Asian (EAS) AF: 0.708 AC: 3657 AN: 5166

South Asian (SAS) AF: 0.446 AC: 2141 AN: 4804

European-Finnish (FIN) AF: 0.674 AC: 7118 AN: 10562

Middle Eastern (MID) AF: 0.747 AC: 218 AN: 292

European-Non Finnish (NFE) AF: 0.708 AC: 48128 AN: 67952

Other (OTH) AF: 0.679 AC: 1428 AN: 2102

Alfa AF: 0.681 Hom.: 6534

Bravo AF: 0.662

Asia WGS AF: 0.570 AC: 1985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.7
DANN	Benign	0.66
PhyloP100		1.3
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: rs10799319; hg19: chr1-225703485; COSMIC: COSV52866224; COSMIC: COSV52866224;