Variant 19-18450783-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006532.4(ELL):c.1159C>T(p.Arg387Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000671 in 1,579,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

ELL
NM_006532.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.303

Variant links:

Genes affected

ELL (HGNC:23114): (elongation factor for RNA polymerase II) Enables phosphatase binding activity. Involved in positive regulation of transcription, DNA-templated and snRNA transcription. Located in cytosol; nuclear body; and transcriptionally active chromatin. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ELL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029178828).

BS2

High AC in GnomAd4 at 39 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELL	NM_006532.4 linkuse as main transcript	c.1159C>T	p.Arg387Trp	missense_variant	8/12	ENST00000262809.9	NP_006523.1	P55199

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ELL	ENST00000262809.9 linkuse as main transcript	c.1159C>T	p.Arg387Trp	missense_variant	8/12	1	NM_006532.4	ENSP00000262809.3	P55199
ELL	ENST00000596124.3 linkuse as main transcript	c.760C>T	p.Arg254Trp	missense_variant	8/12	1		ENSP00000475648.2	U3KQ90
ELL	ENST00000594635.6 linkuse as main transcript	n.*994C>T		non_coding_transcript_exon_variant	9/13	1		ENSP00000475681.2	U3KQA3
ELL	ENST00000594635.6 linkuse as main transcript	n.*994C>T		3_prime_UTR_variant	9/13	1		ENSP00000475681.2	U3KQA3

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000119

AC:

AN:

201476

Hom.:

AF XY:

0.0000727

AC XY:

AN XY:

110050

show subpopulations

Gnomad AFR exome

AF:

0.00108

Gnomad AMR exome

AF:

0.000206

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000631

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000450

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000469

AC:

AN:

1427256

Hom.:

Cov.:

AF XY:

0.0000340

AC XY:

AN XY:

706198

show subpopulations

Gnomad4 AFR exome

AF:

0.00112

Gnomad4 AMR exome

AF:

0.000175

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000772

Gnomad4 SAS exome

AF:

0.0000364

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000128

Gnomad4 OTH exome

AF:

0.0000509

GnomAD4 genome

AF:

0.000256

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.000843

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000493

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.000230

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000101

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.1159C>T (p.R387W) alteration is located in exon 8 (coding exon 8) of the ELL gene. This alteration results from a C to T substitution at nucleotide position 1159, causing the arginine (R) at amino acid position 387 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.048

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.7

N;.

REVEL

Benign

0.080

Sift

Benign

0.18

T;.

Sift4G

Uncertain

0.014

D;D

Polyphen

0.99

D;.

Vest4

0.38

MVP

0.35

MPC

0.071

ClinPred

0.041

GERP RS

-0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.27

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