Genetic Variant NM_018208.4:c.642-75G>A (chr1-204141532-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018208.4(ETNK2):c.642-75G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 1,493,010 control chromosomes in the GnomAD database, including 9,287 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2482 hom., cov: 32)

Exomes 𝑓: 0.092 ( 6805 hom. )

Consequence

ETNK2
NM_018208.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.678

Publications

8 publications found

Variant links:

Genes affected

ETNK2 (HGNC:25575): (ethanolamine kinase 2) The protein encoded by this gene is a member of choline/ethanolamine kinase family which catalyzes the first step of phosphatidylethanolamine (PtdEtn) biosynthesis via the cytidine diphosphate (CDP) ethanolamine pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ETNK2 links:

ERLNC1 (HGNC:41109): (estrogen receptor responsive lncRNA 1)

ERLNC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETNK2	NM_018208.4 link	c.642-75G>A		intron_variant	Intron 3 of 7	ENST00000367202.9	NP_060678.2	Q9NVF9-1A0A024R9A8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETNK2	ENST00000367202.9 link	c.642-75G>A		intron_variant	Intron 3 of 7	1	NM_018208.4	ENSP00000356170.4		Q9NVF9-1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22801

AN:

152076

Hom.:

2472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.0656

Gnomad SAS

AF:

0.0967

Gnomad FIN

AF:

0.0860

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.0862

Gnomad OTH

AF:

0.146

GnomAD4 exome

AF:

0.0920

AC:

123368

AN:

1340816

Hom.:

6805

Cov.:

AF XY:

0.0919

AC XY:

60684

AN XY:

660232

show subpopulations

African (AFR)

AF:

0.317

AC:

9592

AN:

30230

American (AMR)

AF:

0.117

AC:

3928

AN:

33498

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

3315

AN:

23306

East Asian (EAS)

AF:

0.0575

AC:

2028

AN:

35276

South Asian (SAS)

AF:

0.100

AC:

7450

AN:

74330

European-Finnish (FIN)

AF:

0.0778

AC:

3611

AN:

46434

Middle Eastern (MID)

AF:

0.149

AC:

611

AN:

4100

European-Non Finnish (NFE)

AF:

0.0838

AC:

86962

AN:

1037880

Other (OTH)

AF:

0.105

AC:

5871

AN:

55762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

5212

10425

15637

20850

26062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3424

6848

10272

13696

17120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.150

AC:

22827

AN:

152194

Hom.:

2482

Cov.:

AF XY:

0.148

AC XY:

11041

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.302

AC:

12525

AN:

41494

American (AMR)

AF:

0.118

AC:

1804

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

532

AN:

3472

East Asian (EAS)

AF:

0.0649

AC:

337

AN:

5190

South Asian (SAS)

AF:

0.0968

AC:

466

AN:

4814

European-Finnish (FIN)

AF:

0.0860

AC:

913

AN:

10616

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0862

AC:

5861

AN:

68002

Other (OTH)

AF:

0.146

AC:

308

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

931

1862

2794

3725

4656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0942

Hom.:

1520

Bravo

AF:

0.160

Asia WGS

AF:

0.101

AC:

350

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.21

(source)

DANN

Benign

0.23

PhyloP100

-0.68

PromoterAI

-0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over