chr1-225519331-A-ATCCAGGCGTTCCTGCCGC

Variant names:

• chr1-225519331-A-ATCCAGGCGTTCCTGCCGC
• rs71170086
• NM_018212.6:c.651_668dupGCGGCAGGAACGCCTGGA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4 BS1 BS2

The NM_018212.6(ENAH):​c.651_668dupGCGGCAGGAACGCCTGGA​(p.Glu217_Leu222dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 1,610,322 control chromosomes in the GnomAD database, including 162 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0094 (25 hom., cov: 31)
  • Exomes 𝑓: 0.0050 (137 hom.)
• Consequence: ENAH NM_018212.6 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -6 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_018212.6.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00945 (1410/149242) while in subpopulation EAS AF= 0.0451 (223/4948). AF 95% confidence interval is 0.0402. There are 25 homozygotes in gnomad4. There are 709 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1410 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAH	NM_018212.6	c.651_668dupGCGGCAGGAACGCCTGGA	p.Glu217_Leu222dup	disruptive_inframe_insertion	Exon 5 of 14	ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.651_668dupGCGGCAGGAACGCCTGGA	p.Glu217_Leu222dup	disruptive_inframe_insertion	Exon 5 of 14	1	NM_018212.6	ENSP00000355808.2

Frequencies

GnomAD3 genomes AF: 0.00941 AC: 1404 AN: 149148 Hom.: 25 Cov.: 31

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00221

Gnomad AMR AF: 0.00685

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.0450

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.00566

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.00559

Gnomad OTH AF: 0.0118

GnomAD3 exomes AF: 0.00694 AC: 1737 AN: 250234 Hom.: 609 AF XY: 0.00678 AC XY: 918 AN XY: 135350

Gnomad AFR exome AF: 0.00667

Gnomad AMR exome AF: 0.00463

Gnomad ASJ exome AF: 0.00418

Gnomad EAS exome AF: 0.0410

Gnomad SAS exome AF: 0.0121

Gnomad FIN exome AF: 0.00183

Gnomad NFE exome AF: 0.00205

Gnomad OTH exome AF: 0.00589

GnomAD4 exome AF: 0.00501 AC: 7327 AN: 1461080 Hom.: 137 Cov.: 30 AF XY: 0.00590 AC XY: 4292 AN XY: 726894

Gnomad4 AFR exome AF: 0.00559

Gnomad4 AMR exome AF: 0.00425

Gnomad4 ASJ exome AF: 0.0111

Gnomad4 EAS exome AF: 0.0371

Gnomad4 SAS exome AF: 0.0247

Gnomad4 FIN exome AF: 0.00668

Gnomad4 NFE exome AF: 0.00208

Gnomad4 OTH exome AF: 0.00572

GnomAD4 genome AF: 0.00945 AC: 1410 AN: 149242 Hom.: 25 Cov.: 31 AF XY: 0.00974 AC XY: 709 AN XY: 72766

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.00684

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.0451

Gnomad4 SAS AF: 0.0243

Gnomad4 FIN AF: 0.00566

Gnomad4 NFE AF: 0.00559

Gnomad4 OTH AF: 0.0122

ClinVar

Not reported in ClinVar

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;