dbSNP rs6716767: EML4:n.4190A>C (chr2-42332116-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000406175.3(EML4):n.4190A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 220,898 control chromosomes in the GnomAD database, including 2,543 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 ( 2014 hom., cov: 32)

Exomes 𝑓: 0.12 ( 529 hom. )

Consequence

EML4
ENST00000406175.3 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.29

Publications

9 publications found

Variant links:

Genes affected

EML4 (HGNC:1316): (EMAP like 4) This gene is a member of the echinoderm microtubule associated protein-like family. The encoded WD-repeat protein may be involved in microtubule formation. Abnormal fusion of parts of this gene with portions of the anaplastic lymphoma receptor tyrosine kinase gene, which generates EML4-ALK fusion transcripts, is one of the primary mutations associated with non-small cell lung cancer. Alternative splicing of this gene results in two transcript variants. [provided by RefSeq, Jan 2015]

EML4 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=-0.75).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EML4	NM_019063.5 link	c.*1909A>C		3_prime_UTR_variant	Exon 23 of 23	ENST00000318522.10	NP_061936.3	Q9HC35-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EML4	ENST00000406175.3 link	n.4190A>C		non_coding_transcript_exon_variant	Exon 14 of 14	1
EML4	ENST00000318522.10 link	c.*1909A>C		3_prime_UTR_variant	Exon 23 of 23	1	NM_019063.5	ENSP00000320663.5		Q9HC35-1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23075

AN:

152078

Hom.:

2009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0942

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.0292

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.169

GnomAD4 exome

AF:

0.116

AC:

7938

AN:

68704

Hom.:

529

Cov.:

AF XY:

0.115

AC XY:

3643

AN XY:

31816

show subpopulations

African (AFR)

AF:

0.222

AC:

703

AN:

3164

American (AMR)

AF:

0.0915

AC:

190

AN:

2076

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

704

AN:

4350

East Asian (EAS)

AF:

0.0416

AC:

412

AN:

9904

South Asian (SAS)

AF:

0.328

AC:

187

AN:

570

European-Finnish (FIN)

AF:

0.153

AC:

AN:

236

Middle Eastern (MID)

AF:

0.231

AC:

AN:

424

European-Non Finnish (NFE)

AF:

0.114

AC:

4837

AN:

42310

Other (OTH)

AF:

0.136

AC:

771

AN:

5670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

345

690

1034

1379

1724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.152

AC:

23110

AN:

152194

Hom.:

2014

Cov.:

AF XY:

0.154

AC XY:

11449

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.230

AC:

9543

AN:

41490

American (AMR)

AF:

0.0940

AC:

1438

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

623

AN:

3466

East Asian (EAS)

AF:

0.0287

AC:

149

AN:

5194

South Asian (SAS)

AF:

0.300

AC:

1447

AN:

4816

European-Finnish (FIN)

AF:

0.139

AC:

1477

AN:

10602

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.116

AC:

7923

AN:

68012

Other (OTH)

AF:

0.175

AC:

370

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

975

1950

2926

3901

4876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.130

Hom.:

2545

Bravo

AF:

0.148

Asia WGS

AF:

0.178

AC:

619

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.4

(source)

DANN

Benign

0.82

PhyloP100

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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