Variant 19-18450663-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006532.4(ELL):c.1279C>T(p.Leu427Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,591,648 control chromosomes in the GnomAD database, including 213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 95 hom., cov: 33)

Exomes 𝑓: 0.0085 ( 118 hom. )

Consequence

ELL
NM_006532.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.58

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-18450663-G-A is Benign according to our data. Variant chr19-18450663-G-A is described in ClinVar as [Benign]. Clinvar id is 1304815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.58 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELL	NM_006532.4 linkuse as main transcript	c.1279C>T	p.Leu427Leu	synonymous_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.1279C>T	p.Leu427Leu	synonymous_variant	8/12	1	NM_006532.4	ENSP00000262809.3	P55199
ELL	ENST00000596124.3 linkuse as main transcript	c.880C>T	p.Leu294Leu	synonymous_variant	8/12	1		ENSP00000475648.2	U3KQ90
ELL	ENST00000594635.6 linkuse as main transcript	n.*1114C>T		non_coding_transcript_exon_variant	9/13	1		ENSP00000475681.2	U3KQA3
ELL	ENST00000594635.6 linkuse as main transcript	n.*1114C>T		3_prime_UTR_variant	9/13	1		ENSP00000475681.2	U3KQA3

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

3635

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0661

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0146

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00631

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00772

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.00972

AC:

1963

AN:

202030

Hom.:

AF XY:

0.00834

AC XY:

921

AN XY:

110368

show subpopulations

Gnomad AFR exome

AF:

0.0685

Gnomad AMR exome

AF:

0.00723

Gnomad ASJ exome

AF:

0.00810

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000577

Gnomad FIN exome

AF:

0.00601

Gnomad NFE exome

AF:

0.00813

Gnomad OTH exome

AF:

0.00689

GnomAD4 exome

AF:

0.00855

AC:

12304

AN:

1439360

Hom.:

118

Cov.:

AF XY:

0.00817

AC XY:

5834

AN XY:

714464

show subpopulations

Gnomad4 AFR exome

AF:

0.0696

Gnomad4 AMR exome

AF:

0.00749

Gnomad4 ASJ exome

AF:

0.00736

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000510

Gnomad4 FIN exome

AF:

0.00691

Gnomad4 NFE exome

AF:

0.00762

Gnomad4 OTH exome

AF:

0.0109

GnomAD4 genome

AF:

0.0240

AC:

3657

AN:

152288

Hom.:

Cov.:

AF XY:

0.0230

AC XY:

1710

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0664

Gnomad4 AMR

AF:

0.0146

Gnomad4 ASJ

AF:

0.00835

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00631

Gnomad4 NFE

AF:

0.00772

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.00816

Hom.:

Bravo

AF:

0.0264

Asia WGS

AF:

0.00837

AC:

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 22, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.4

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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