19-18451628-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006532.4(ELL):c.890G>A(p.Ser297Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,504,256 control chromosomes in the GnomAD database, including 15,107 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (1686 hom., cov: 34)
  • Exomes 𝑓: 0.14 (13421 hom.)
• Consequence: ELL NM_006532.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0520

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001521647).
• BP6: Variant 19-18451628-C-T is Benign according to our data. Variant chr19-18451628-C-T is described in ClinVar as [Benign]. Clinvar id is 1227416.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELL	NM_006532.4	c.890G>A	p.Ser297Asn	missense_variant	7/12	ENST00000262809.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELL	ENST00000262809.9	c.890G>A	p.Ser297Asn	missense_variant	7/12	1	NM_006532.4	P1
ELL	ENST00000596124.3	c.491G>A	p.Ser164Asn	missense_variant	7/12	1
ELL	ENST00000594635.6	c.*725G>A		3_prime_UTR_variant, NMD_transcript_variant	8/13	1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22018 AN: 152080 Hom.: 1681 Cov.: 34

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0929

Gnomad ASJ AF: 0.0850

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.123

GnomAD3 exomes AF: 0.132 AC: 14597 AN: 110266 Hom.: 1083 AF XY: 0.139 AC XY: 8330 AN XY: 60000

Gnomad AFR exome AF: 0.173

Gnomad AMR exome AF: 0.0663

Gnomad ASJ exome AF: 0.0861

Gnomad EAS exome AF: 0.0804

Gnomad SAS exome AF: 0.204

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.138 AC: 186195 AN: 1352058 Hom.: 13421 Cov.: 33 AF XY: 0.139 AC XY: 92631 AN XY: 667114

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.0721

Gnomad4 ASJ exome AF: 0.0868

Gnomad4 EAS exome AF: 0.0720

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.145 AC: 22037 AN: 152198 Hom.: 1686 Cov.: 34 AF XY: 0.145 AC XY: 10813 AN XY: 74408

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.0927

Gnomad4 ASJ AF: 0.0850

Gnomad4 EAS AF: 0.0904

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.122

Alfa AF: 0.128 Hom.: 227

Bravo AF: 0.139

TwinsUK AF: 0.146 AC: 541

ALSPAC AF: 0.134 AC: 517

ESP6500AA AF: 0.155 AC: 611

ESP6500EA AF: 0.110 AC: 830

ExAC AF: 0.0818 AC: 4985

Asia WGS AF: 0.154 AC: 533 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 08, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.4
Dann	Benign	0.11
DEOGEN2	Benign	0.067	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.42	T;T
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.46	N;.
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.98	N;.
REVEL	Benign	0.046
Sift	Benign	1.0	T;.
Sift4G	Benign	0.73	T;T
Polyphen		0.0	B;.
Vest4		0.032
MPC		0.018
ClinPred		0.00018	T
GERP RS		-0.84
Varity_R		0.036
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs2303694; hg19: chr19-18562438; COSMIC: COSV53211465; COSMIC: COSV53211465;