rs1075364

Variant names:

• chr1-225627933-C-T
• rs1075364
• NM_018212.6:c.5+24753G>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.5+24753G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 147,100 control chromosomes in the GnomAD database, including 29,583 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 0.64 (29583 hom., cov: 31)
• Consequence: ENAH NM_018212.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAH	NM_018212.6	c.5+24753G>A		intron_variant	Intron 1 of 13	ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.5+24753G>A		intron_variant	Intron 1 of 13	1	NM_018212.6	ENSP00000355808.2
ENAH	ENST00000366844.7	c.5+24753G>A		intron_variant	Intron 1 of 14	1		ENSP00000355809.2
ENAH	ENST00000635051.1	c.5+24753G>A		intron_variant	Intron 1 of 14	5		ENSP00000489607.1
ENAH	ENST00000284563.7	c.5+24753G>A		intron_variant	Intron 1 of 5	5		ENSP00000284563.7

Frequencies

GnomAD3 genomes AF: 0.641 AC: 94206 AN: 146992 Hom.: 29549 Cov.: 31

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.470

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.641 AC: 94291 AN: 147100 Hom.: 29583 Cov.: 31 AF XY: 0.644 AC XY: 46187 AN XY: 71770

African (AFR) AF: 0.726 AC: 29935 AN: 41228

American (AMR) AF: 0.617 AC: 9279 AN: 15038

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1686 AN: 3306

East Asian (EAS) AF: 0.683 AC: 3489 AN: 5112

South Asian (SAS) AF: 0.706 AC: 3199 AN: 4534

European-Finnish (FIN) AF: 0.657 AC: 6322 AN: 9622

Middle Eastern (MID) AF: 0.465 AC: 133 AN: 286

European-Non Finnish (NFE) AF: 0.591 AC: 38440 AN: 65084

Other (OTH) AF: 0.627 AC: 1265 AN: 2018

Alfa AF: 0.621 Hom.: 38559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.1
DANN	Benign	0.42
PhyloP100		-2.0
Mutation Taster		=13/87	disease causing (long InDel)

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: rs1075364; hg19: chr1-225815635; COSMIC: COSV52866372;