5-95905518-T-C

Position:

• chr5-95905518-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ELL2	NM_012081.6	c.741+1005A>G		intron_variant		ENST00000237853.9	NP_036213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELL2	ENST00000237853.9	c.741+1005A>G		intron_variant		1	NM_012081.6	ENSP00000237853.4
ELL2	ENST00000513343.1	c.196-4438A>G		intron_variant		3		ENSP00000423915.1

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

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.346

Alfa AF: 0.312 Hom.: 3424

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

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: rs10069748; hg19: chr5-95241222;