chr1-225519331-ATCCAGGCGTTCCTGCCGC-A

Variant names:

• chr1-225519331-ATCCAGGCGTTCCTGCCGC-A
• rs71170086
• NM_018212.6:c.651_668delGCGGCAGGAACGCCTGGA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_018212.6(ENAH):​c.651_668delGCGGCAGGAACGCCTGGA​(p.Glu217_Leu222del) variant causes a disruptive 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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.04
• 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 -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 VariationId is 767753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 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.651_668delGCGGCAGGAACGCCTGGA	p.Glu217_Leu222del	disruptive_inframe_deletion	Exon 5 of 14	NP_060682.2
	ENAH	NM_001420159.1		c.708_725delGCGGCAGGAACGCCTGGA	p.Glu236_Leu241del	disruptive_inframe_deletion	Exon 6 of 16	NP_001407088.1
	ENAH	NM_001420160.1		c.651_668delGCGGCAGGAACGCCTGGA	p.Glu217_Leu222del	disruptive_inframe_deletion	Exon 5 of 15	NP_001407089.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENAH	ENST00000366843.7	TSL:1 MANE Select	c.651_668delGCGGCAGGAACGCCTGGA	p.Glu217_Leu222del	disruptive_inframe_deletion	Exon 5 of 14	ENSP00000355808.2	Q8N8S7-2
	ENAH	ENST00000366844.7	TSL:1	c.651_668delGCGGCAGGAACGCCTGGA	p.Glu217_Leu222del	disruptive_inframe_deletion	Exon 5 of 15	ENSP00000355809.2	Q8N8S7-1
	ENAH	ENST00000497899.6	TSL:1	c.501_518delGCGGCAGGAACGCCTGGA	p.Glu167_Leu172del	disruptive_inframe_deletion	Exon 4 of 4	ENSP00000489106.1	A0A0U1RQP7

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

GnomAD2 exomes AF: 0.0394 AC: 9852 AN: 250234 AF XY: 0.0377

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 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

African (AFR) AF: 0.0310 AC: 1035 AN: 33430

American (AMR) AF: 0.0421 AC: 1881 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0790 AC: 2065 AN: 26126

East Asian (EAS) AF: 0.0302 AC: 1198 AN: 39682

South Asian (SAS) AF: 0.0579 AC: 4991 AN: 86150

European-Finnish (FIN) AF: 0.0569 AC: 3032 AN: 53296

Middle Eastern (MID) AF: 0.0502 AC: 289 AN: 5756

European-Non Finnish (NFE) AF: 0.0358 AC: 39842 AN: 1111516

Other (OTH) AF: 0.0540 AC: 3258 AN: 60356

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

African (AFR) AF: 0.0701 AC: 2838 AN: 40508

American (AMR) AF: 0.104 AC: 1562 AN: 15042

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 512 AN: 3400

East Asian (EAS) AF: 0.0396 AC: 196 AN: 4946

South Asian (SAS) AF: 0.0959 AC: 437 AN: 4556

European-Finnish (FIN) AF: 0.0719 AC: 737 AN: 10246

Middle Eastern (MID) AF: 0.148 AC: 43 AN: 290

European-Non Finnish (NFE) AF: 0.113 AC: 7626 AN: 67210

Other (OTH) AF: 0.111 AC: 229 AN: 2054

Alfa AF: 0.0510 Hom.: 111

Bravo AF: 0.0963

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=188/12	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs71170086; hg19: chr1-225707033; COSMIC: COSV52866997; COSMIC: COSV52866997;