rs4808801

Positions:

• chr19-18460331-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006532.4(ELL):​c.744+1247T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,068 control chromosomes in the GnomAD database, including 16,657 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 0.44 (16657 hom., cov: 32)
• Consequence: ELL NM_006532.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELL	NM_006532.4	c.744+1247T>C		intron_variant		ENST00000262809.9	NP_006523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELL	ENST00000262809.9	c.744+1247T>C		intron_variant		1	NM_006532.4	ENSP00000262809.3
ELL	ENST00000596124.3	c.345+1247T>C		intron_variant		1		ENSP00000475648.2
ELL	ENST00000594635.6	n.*579+1247T>C		intron_variant		1		ENSP00000475681.2

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66938 AN: 151950 Hom.: 16624 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.441 AC: 67022 AN: 152068 Hom.: 16657 Cov.: 32 AF XY: 0.439 AC XY: 32654 AN XY: 74334

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.409

Alfa AF: 0.372 Hom.: 7437

Bravo AF: 0.448

Asia WGS AF: 0.404 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.37

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

Other links and lift over

dbSNP: rs4808801; hg19: chr19-18571141;