rs731945

Variant names:

• chr19-18456229-C-T
• rs731945
• NM_006532.4:c.869+1976G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006532.4(ELL):​c.869+1976G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,098 control chromosomes in the GnomAD database, including 7,147 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 0.28 (7147 hom., cov: 32)
• Consequence: ELL NM_006532.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELL	NM_006532.4	c.869+1976G>A		intron_variant	Intron 6 of 11	ENST00000262809.9	NP_006523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELL	ENST00000262809.9	c.869+1976G>A		intron_variant	Intron 6 of 11	1	NM_006532.4	ENSP00000262809.3
ELL	ENST00000596124.3	c.470+1976G>A		intron_variant	Intron 6 of 11	1		ENSP00000475648.2
ELL	ENST00000594635.6	n.*704+1976G>A		intron_variant	Intron 7 of 12	1		ENSP00000475681.2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42418 AN: 151982 Hom.: 7142 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.314

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.279 AC: 42440 AN: 152098 Hom.: 7147 Cov.: 32 AF XY: 0.286 AC XY: 21283 AN XY: 74346

African (AFR) AF: 0.108 AC: 4497 AN: 41504

American (AMR) AF: 0.399 AC: 6097 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1268 AN: 3468

East Asian (EAS) AF: 0.628 AC: 3247 AN: 5168

South Asian (SAS) AF: 0.321 AC: 1547 AN: 4822

European-Finnish (FIN) AF: 0.366 AC: 3865 AN: 10554

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20887 AN: 67966

Other (OTH) AF: 0.311 AC: 659 AN: 2116

Alfa AF: 0.308 Hom.: 16359

Bravo AF: 0.278

Asia WGS AF: 0.432 AC: 1506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.24
DANN	Benign	0.53
PhyloP100		-0.70
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

Other links and lift over

dbSNP: rs731945; hg19: chr19-18567039;