rs139959604

Variant names:

• chr1-225498336-CA-C
• rs139959604
• NM_018212.6:c.1675+10delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018212.6(ENAH):​c.1675+10delT 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
• Publications: 1 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 -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2138 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAH	NM_018212.6	c.1675+10delT		intron_variant	Intron 13 of 13	ENST00000366843.7	NP_060682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7	c.1675+10delT		intron_variant	Intron 13 of 13	1	NM_018212.6	ENSP00000355808.2

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

GnomAD2 exomes AF: 0.00640 AC: 1537 AN: 239996 AF XY: 0.00638

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 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

African (AFR) AF: 0.0467 AC: 1499 AN: 32124

American (AMR) AF: 0.00399 AC: 167 AN: 41854

Ashkenazi Jewish (ASJ) AF: 0.0000388 AC: 1 AN: 25754

East Asian (EAS) AF: 0.0000764 AC: 3 AN: 39274

South Asian (SAS) AF: 0.0219 AC: 1807 AN: 82680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53276

Middle Eastern (MID) AF: 0.00545 AC: 31 AN: 5688

European-Non Finnish (NFE) AF: 0.000281 AC: 307 AN: 1091528

Other (OTH) AF: 0.00445 AC: 264 AN: 59388

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

African (AFR) AF: 0.0460 AC: 1908 AN: 41518

American (AMR) AF: 0.00438 AC: 67 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0215 AC: 103 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 67990

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

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

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs139959604; hg19: chr1-225686038;