1-225519569-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018212.6(ENAH):c.435-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,198,958 control chromosomes in the GnomAD database, including 126 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (125 hom., cov: 31)
  • Exomes 𝑓: 0.14 (1 hom.)
• Consequence: ENAH NM_018212.6 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0170

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 -10 ACMG points.

• BP6: Variant 1-225519569-GA-G is Benign according to our data. Variant chr1-225519569-GA-G is described in ClinVar as [Benign]. Clinvar id is 218481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENAH	NM_018212.6	c.435-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000366843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENAH	ENST00000366843.7	c.435-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018212.6	P2

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 3506 AN: 127006 Hom.: 124 Cov.: 31

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.0156

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00323

Gnomad EAS AF: 0.00549

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.00600

Gnomad MID AF: 0.0189

Gnomad NFE AF: 0.00285

Gnomad OTH AF: 0.0271

GnomAD4 exome AF: 0.139 AC: 148719 AN: 1071938 Hom.: 1 Cov.: 0 AF XY: 0.144 AC XY: 76690 AN XY: 534004

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.0277 AC: 3517 AN: 127020 Hom.: 125 Cov.: 31 AF XY: 0.0285 AC XY: 1730 AN XY: 60702

Gnomad4 AFR AF: 0.0858

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00323

Gnomad4 EAS AF: 0.00551

Gnomad4 SAS AF: 0.0264

Gnomad4 FIN AF: 0.00600

Gnomad4 NFE AF: 0.00285

Gnomad4 OTH AF: 0.0286

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Jul 17, 2015

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Computational scores

Source: dbNSFP v4.3

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: rs34432111; hg19: chr1-225707271;