1-225519569-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_018212.6(ENAH):c.435-4C>T 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 0.000549 in 1,364,700 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00055 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENAH NM_018212.6 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003052
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0910

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-225519569-G-A is Benign according to our data. Variant chr1-225519569-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 790252.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENAH	NM_018212.6	c.435-4C>T		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.435-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_018212.6	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 39 AN: 127100 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.000116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000245

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00345

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000549 AC: 749 AN: 1364700 Hom.: 2 Cov.: 55 AF XY: 0.000582 AC XY: 394 AN XY: 677218

Gnomad4 AFR exome AF: 0.00190

Gnomad4 AMR exome AF: 0.00146

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.000632

Gnomad4 NFE exome AF: 0.000394

Gnomad4 OTH exome AF: 0.000794

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000307 AC: 39 AN: 127100 Hom.: 0 Cov.: 31 AF XY: 0.000494 AC XY: 30 AN XY: 60730

Gnomad4 AFR AF: 0.000116

Gnomad4 AMR AF: 0.000245

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00345

Gnomad4 NFE AF: 0.000152

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00187 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.72
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000031
dbscSNV1_RF	Benign	0.016
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: rs1268170581; hg19: chr1-225707271; COSMIC: COSV52869912; COSMIC: COSV52869912;