5-95905518-T-C

Variant names:

• chr5-95905518-T-C
• rs10069748
• NM_012081.6:c.741+1005A>G

Variant summary

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

The NM_012081.6(ELL2):​c.741+1005A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,694 control chromosomes in the GnomAD database, including 11,828 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 0.37 (11828 hom., cov: 31)
• Consequence: ELL2 NM_012081.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753
• Publications: 12 publications found

Genes affected

ELL2 (HGNC:17064): (elongation factor for RNA polymerase II 2) Involved in snRNA transcription by RNA polymerase II. Located in nucleoplasm. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000250362 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELL2	NM_012081.6	c.741+1005A>G		intron_variant	Intron 5 of 11	ENST00000237853.9	NP_036213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELL2	ENST00000237853.9	c.741+1005A>G		intron_variant	Intron 5 of 11	1	NM_012081.6	ENSP00000237853.4
ELL2	ENST00000513343.1	c.196-4438A>G		intron_variant	Intron 2 of 4	3		ENSP00000423915.1
ENSG00000250362	ENST00000718070.1	n.740-25153T>C		intron_variant	Intron 4 of 5
ENSG00000250362	ENST00000718072.1	n.738-1795T>C		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56465 AN: 151578 Hom.: 11792 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.373 AC: 56540 AN: 151694 Hom.: 11828 Cov.: 31 AF XY: 0.373 AC XY: 27644 AN XY: 74116

African (AFR) AF: 0.577 AC: 23805 AN: 41256

American (AMR) AF: 0.325 AC: 4952 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3464

East Asian (EAS) AF: 0.439 AC: 2262 AN: 5150

South Asian (SAS) AF: 0.427 AC: 2057 AN: 4820

European-Finnish (FIN) AF: 0.293 AC: 3081 AN: 10522

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

European-Non Finnish (NFE) AF: 0.272 AC: 18502 AN: 67920

Other (OTH) AF: 0.346 AC: 730 AN: 2110

Alfa AF: 0.357 Hom.: 8074

Bravo AF: 0.386

Asia WGS AF: 0.443 AC: 1540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.6
DANN	Benign	0.72
PhyloP100		0.75
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: rs10069748; hg19: chr5-95241222;