rs16938747

Variant names:

• chr8-73966852-C-G
• rs16938747
• NM_005648.4:c.-51+5225G>C

Variant summary

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

The NM_005648.4(ELOC):​c.-51+5225G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 152,140 control chromosomes in the GnomAD database, including 346 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 0.047 (346 hom., cov: 31)
• Consequence: ELOC NM_005648.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005648.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELOC	NM_005648.4	MANE Select	c.-51+5225G>C		intron	N/A	NP_005639.1	Q15369-1
	ELOC	NM_001204857.2		c.-51+5393G>C		intron	N/A	NP_001191786.1	Q15369-1
	ELOC	NM_001204858.2		c.-193-2223G>C		intron	N/A	NP_001191787.1	Q15369-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELOC	ENST00000520242.6	TSL:1 MANE Select	c.-51+5225G>C		intron	N/A	ENSP00000428171.1	Q15369-1
	ELOC	ENST00000518127.5	TSL:1	c.-51+5393G>C		intron	N/A	ENSP00000428334.1	Q15369-1
	ELOC	ENST00000520210.1	TSL:1	c.-45+5225G>C		intron	N/A	ENSP00000430224.1	Q15369-2

Frequencies

GnomAD3 genomes AF: 0.0469 AC: 7127 AN: 152022 Hom.: 347 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00704

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0157

Gnomad OTH AF: 0.0407

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

GnomAD4 genome AF: 0.0470 AC: 7146 AN: 152140 Hom.: 346 Cov.: 31 AF XY: 0.0455 AC XY: 3388 AN XY: 74406

African (AFR) AF: 0.128 AC: 5296 AN: 41462

American (AMR) AF: 0.0206 AC: 315 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00705 AC: 34 AN: 4826

European-Finnish (FIN) AF: 0.0179 AC: 190 AN: 10608

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0157 AC: 1066 AN: 68006

Other (OTH) AF: 0.0403 AC: 85 AN: 2110

Alfa AF: 0.0394 Hom.: 29

Bravo AF: 0.0508

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.84
DANN	Benign	0.63
PhyloP100		-0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs16938747; hg19: chr8-74879087;