5-95907227-T-C

Position:

• chr5-95907227-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.482-445A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 148,872 control chromosomes in the GnomAD database, including 6,832 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 0.30 (6832 hom., cov: 28)
• Consequence: ELL2 NM_012081.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELL2	NM_012081.6	c.482-445A>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.482-445A>G		intron_variant		1	NM_012081.6	ENSP00000237853	P1
ELL2	ENST00000513343.1	c.196-6147A>G		intron_variant		3		ENSP00000423915
ELL2	ENST00000506628.1	n.262-445A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.297 AC: 44202 AN: 148796 Hom.: 6823 Cov.: 28

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.297 AC: 44228 AN: 148872 Hom.: 6832 Cov.: 28 AF XY: 0.296 AC XY: 21505 AN XY: 72616

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.284

Alfa AF: 0.271 Hom.: 626

Bravo AF: 0.303

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.1
DANN	Benign	0.31

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: rs56219066; hg19: chr5-95242931;