1-225498336-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018212.6(ENAH):c.1675+10del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,583,730 control chromosomes in the GnomAD database, including 131 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (50 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (81 hom.)
• Consequence: ENAH NM_018212.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.316

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 1-225498336-CA-C is Benign according to our data. Variant chr1-225498336-CA-C is described in ClinVar as [Benign]. Clinvar id is 780300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2138/152164) while in subpopulation AFR AF= 0.046 (1908/41518). AF 95% confidence interval is 0.0442. There are 50 homozygotes in gnomad4. There are 1074 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 2124 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENAH	NM_018212.6	c.1675+10del		intron_variant		ENST00000366843.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENAH	ENST00000366843.7	c.1675+10del		intron_variant		1	NM_018212.6	P2

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2124 AN: 152046 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.00640 AC: 1537 AN: 239996 Hom.: 36 AF XY: 0.00638 AC XY: 828 AN XY: 129696

Gnomad AFR exome AF: 0.0448

Gnomad AMR exome AF: 0.00393

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.000396

Gnomad SAS exome AF: 0.0228

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000426

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00285 AC: 4079 AN: 1431566 Hom.: 81 Cov.: 26 AF XY: 0.00332 AC XY: 2365 AN XY: 713128

Gnomad4 AFR exome AF: 0.0467

Gnomad4 AMR exome AF: 0.00399

Gnomad4 ASJ exome AF: 0.0000388

Gnomad4 EAS exome AF: 0.0000764

Gnomad4 SAS exome AF: 0.0219

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000281

Gnomad4 OTH exome AF: 0.00445

GnomAD4 genome AF: 0.0141 AC: 2138 AN: 152164 Hom.: 50 Cov.: 32 AF XY: 0.0144 AC XY: 1074 AN XY: 74396

Gnomad4 AFR AF: 0.0460

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0215

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.000742 Hom.: 0

Bravo AF: 0.0148

Asia WGS AF: 0.0110 AC: 38 AN: 3474

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

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: rs139959604; hg19: chr1-225686038;