rs10915846

Variant names:

• chr1-225523485-G-A
• rs10915846
• NM_018212.6:c.435-3920C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-225523485-G-A
• chr1-225523485-G-C
• chr1-225523485-G-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.435-3920C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 151,868 control chromosomes in the GnomAD database, including 3,931 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 0.20 (3931 hom., cov: 31)
• Consequence: ENAH NM_018212.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018212.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENAH	NM_018212.6	MANE Select	c.435-3920C>T		intron	N/A	NP_060682.2
	ENAH	NM_001420159.1		c.492-3920C>T		intron	N/A	NP_001407088.1
	ENAH	NM_001420160.1		c.435-3920C>T		intron	N/A	NP_001407089.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENAH	ENST00000366843.7	TSL:1 MANE Select	c.435-3920C>T		intron	N/A	ENSP00000355808.2	Q8N8S7-2
	ENAH	ENST00000366844.7	TSL:1	c.435-3920C>T		intron	N/A	ENSP00000355809.2	Q8N8S7-1
	ENAH	ENST00000497899.6	TSL:1	c.285-3920C>T		intron	N/A	ENSP00000489106.1	A0A0U1RQP7

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30993 AN: 151750 Hom.: 3931 Cov.: 31

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.204 AC: 30986 AN: 151868 Hom.: 3931 Cov.: 31 AF XY: 0.201 AC XY: 14877 AN XY: 74170

African (AFR) AF: 0.0514 AC: 2132 AN: 41498

American (AMR) AF: 0.291 AC: 4442 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1260 AN: 3462

East Asian (EAS) AF: 0.169 AC: 867 AN: 5124

South Asian (SAS) AF: 0.114 AC: 549 AN: 4810

European-Finnish (FIN) AF: 0.187 AC: 1960 AN: 10502

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18956 AN: 67922

Other (OTH) AF: 0.236 AC: 496 AN: 2104

Alfa AF: 0.232 Hom.: 2329

Bravo AF: 0.207

Asia WGS AF: 0.117 AC: 405 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.34
PhyloP100		-0.0020
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: rs10915846; hg19: chr1-225711187;