1-225519331-ATCCAGGCGTTCCTGCCGC-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_018212.6(ENAH):c.651_668del(p.Glu217_Leu222del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 1,610,184 control chromosomes in the GnomAD database, including 6,841 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.096 (748 hom., cov: 31)
  • Exomes 𝑓: 0.039 (6093 hom.)
• Consequence: ENAH NM_018212.6 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.04

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 -8 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_018212.6.
• BP6: Variant 1-225519331-ATCCAGGCGTTCCTGCCGC-A is Benign according to our data. Variant chr1-225519331-ATCCAGGCGTTCCTGCCGC-A is described in ClinVar as [Benign]. Clinvar id is 767753.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-225519331-ATCCAGGCGTTCCTGCCGC-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENAH	NM_018212.6	c.651_668del	p.Glu217_Leu222del	inframe_deletion	5/14	ENST00000366843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENAH	ENST00000366843.7	c.651_668del	p.Glu217_Leu222del	inframe_deletion	5/14	1	NM_018212.6	P2

Frequencies

GnomAD3 genomes AF: 0.0959 AC: 14299 AN: 149062 Hom.: 748 Cov.: 31

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.0719

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.0394 AC: 9852 AN: 250234 Hom.: 725 AF XY: 0.0377 AC XY: 5101 AN XY: 135350

Gnomad AFR exome AF: 0.0299

Gnomad AMR exome AF: 0.0482

Gnomad ASJ exome AF: 0.0611

Gnomad EAS exome AF: 0.0231

Gnomad SAS exome AF: 0.0424

Gnomad FIN exome AF: 0.0309

Gnomad NFE exome AF: 0.0382

Gnomad OTH exome AF: 0.0633

GnomAD4 exome AF: 0.0394 AC: 57591 AN: 1461028 Hom.: 6093 AF XY: 0.0422 AC XY: 30675 AN XY: 726868

Gnomad4 AFR exome AF: 0.0310

Gnomad4 AMR exome AF: 0.0421

Gnomad4 ASJ exome AF: 0.0790

Gnomad4 EAS exome AF: 0.0302

Gnomad4 SAS exome AF: 0.0579

Gnomad4 FIN exome AF: 0.0569

Gnomad4 NFE exome AF: 0.0358

Gnomad4 OTH exome AF: 0.0540

GnomAD4 genome AF: 0.0959 AC: 14304 AN: 149156 Hom.: 748 Cov.: 31 AF XY: 0.0927 AC XY: 6739 AN XY: 72716

Gnomad4 AFR AF: 0.0701

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0396

Gnomad4 SAS AF: 0.0959

Gnomad4 FIN AF: 0.0719

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.111

Bravo AF: 0.0963

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71170086; hg19: chr1-225707033;