NM_005648.4:c.-50-5298A>G

Variant names:

• chr8-73965116-T-C
• rs2433208
• NM_005648.4:c.-50-5298A>G

Variant summary

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

The NM_005648.4(ELOC):​c.-50-5298A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 146,728 control chromosomes in the GnomAD database, including 778 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 0.089 (778 hom., cov: 31)
• Consequence: ELOC NM_005648.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.673
• Publications: 5 publications found

Genes affected

ELOC (HGNC:11617): (elongin C) This gene encodes the protein elongin C, which is a subunit of the transcription factor B (SIII) complex. The SIII complex is composed of elongins A/A2, B and C. It activates elongation by RNA polymerase II by suppressing transient pausing of the polymerase at many sites within transcription units. Elongin A functions as the transcriptionally active component of the SIII complex, whereas elongins B and C are regulatory subunits. Elongin A2 is specifically expressed in the testis, and capable of forming a stable complex with elongins B and C. The von Hippel-Lindau tumor suppressor protein binds to elongins B and C, and thereby inhibits transcription elongation. Multiple alternatively spliced transcript variants encoding two distinct isoforms have been identified. [provided by RefSeq, Mar 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELOC	NM_005648.4	c.-50-5298A>G		intron_variant	Intron 1 of 3	ENST00000520242.6	NP_005639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELOC	ENST00000520242.6	c.-50-5298A>G		intron_variant	Intron 1 of 3	1	NM_005648.4	ENSP00000428171.1

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13029 AN: 146668 Hom.: 779 Cov.: 31

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0780

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.000596

Gnomad SAS AF: 0.0716

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0662

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0780

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

GnomAD4 genome AF: 0.0888 AC: 13023 AN: 146728 Hom.: 778 Cov.: 31 AF XY: 0.0908 AC XY: 6470 AN XY: 71262

African (AFR) AF: 0.0199 AC: 792 AN: 39716

American (AMR) AF: 0.0779 AC: 1148 AN: 14736

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 508 AN: 3428

East Asian (EAS) AF: 0.000598 AC: 3 AN: 5020

South Asian (SAS) AF: 0.0710 AC: 331 AN: 4662

European-Finnish (FIN) AF: 0.183 AC: 1679 AN: 9186

Middle Eastern (MID) AF: 0.0679 AC: 19 AN: 280

European-Non Finnish (NFE) AF: 0.124 AC: 8274 AN: 66766

Other (OTH) AF: 0.0773 AC: 158 AN: 2044

Alfa AF: 0.101 Hom.: 1744

Bravo AF: 0.0748

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.8
DANN	Benign	0.45
PhyloP100		0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2433208; hg19: chr8-74877351;