Genetic Variant ELP1:c.1643+145G>A (chr9-108906158-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003640.5(ELP1):c.1643+145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 764,234 control chromosomes in the GnomAD database, including 11,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3466 hom., cov: 32)

Exomes 𝑓: 0.15 ( 7977 hom. )

Consequence

ELP1
NM_003640.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.702

Variant links:

Genes affected

ELP1 (HGNC:5959): (elongator acetyltransferase complex subunit 1) The protein encoded by this gene is a scaffold protein and a regulator for three different kinases involved in proinflammatory signaling. The encoded protein can bind NF-kappa-B-inducing kinase and I-kappa-B kinases through separate domains and assemble them into an active kinase complex. Mutations in this gene have been associated with familial dysautonomia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

ELP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 9-108906158-C-T is Benign according to our data. Variant chr9-108906158-C-T is described in ClinVar as [Benign]. Clinvar id is 1229125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ELP1	NM_003640.5 link	c.1643+145G>A	intron_variant	Intron 14 of 36	ENST00000374647.10	NP_003631.2	O95163Q4LE38Q8N516
ELP1	NM_001318360.2 link	c.1301+145G>A	intron_variant	Intron 14 of 36		NP_001305289.1	O95163A0A6Q8PGW3B4E3I9
ELP1	NM_001330749.2 link	c.596+145G>A	intron_variant	Intron 12 of 34		NP_001317678.1	F5H2T0B3KNB2
ELP1	XM_047423991.1 link	c.1643+145G>A	intron_variant	Intron 14 of 24		XP_047279947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10 link	c.1643+145G>A		intron_variant	Intron 14 of 36	1	NM_003640.5	ENSP00000363779.5		O95163

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29583

AN:

151956

Hom.:

3456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.314

Gnomad AMI

AF:

0.283

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.0626

Gnomad EAS

AF:

0.285

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.124

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.172

GnomAD4 exome

AF:

0.150

AC:

91775

AN:

612158

Hom.:

7977

AF XY:

0.149

AC XY:

48188

AN XY:

324410

show subpopulations

Gnomad4 AFR exome

AF:

0.316

AC:

5184

AN:

16388

Gnomad4 AMR exome

AF:

0.234

AC:

7087

AN:

30316

Gnomad4 ASJ exome

AF:

0.0696

AC:

1269

AN:

18226

Gnomad4 EAS exome

AF:

0.288

AC:

9436

AN:

32750

Gnomad4 SAS exome

AF:

0.173

AC:

9931

AN:

57364

Gnomad4 FIN exome

AF:

0.160

AC:

6122

AN:

38232

Gnomad4 NFE exome

AF:

0.124

AC:

47707

AN:

384316

Gnomad4 Remaining exome

AF:

0.149

AC:

4769

AN:

31934

Heterozygous variant carriers

3565

7129

10694

14258

17823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

858

1716

2574

3432

4290

<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:

0.195

AC:

29629

AN:

152076

Hom.:

3466

Cov.:

AF XY:

0.197

AC XY:

14633

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.315

AC:

0.314828

AN:

0.314828

Gnomad4 AMR

AF:

0.193

AC:

0.193219

AN:

0.193219

Gnomad4 ASJ

AF:

0.0626

AC:

0.0626082

AN:

0.0626082

Gnomad4 EAS

AF:

0.285

AC:

0.284693

AN:

0.284693

Gnomad4 SAS

AF:

0.201

AC:

0.200954

AN:

0.200954

Gnomad4 FIN

AF:

0.165

AC:

0.165438

AN:

0.165438

Gnomad4 NFE

AF:

0.126

AC:

0.125982

AN:

0.125982

Gnomad4 OTH

AF:

0.170

AC:

0.170455

AN:

0.170455

Heterozygous variant carriers

1169

2338

3508

4677

5846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.144

Hom.:

985

Bravo

AF:

0.207

Asia WGS

AF:

0.255

AC:

888

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.0

DANN

Benign

0.52

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over