rs1718866

Variant names:

• chr4-57017009-G-A
• rs1718866
• NM_000938.3:c.1956-34G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-57017009-G-A
• chr4-57017009-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000938.3(POLR2B):​c.1956-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POLR2B NM_000938.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 5 publications found

Genes affected

POLR2B (HGNC:9188): (RNA polymerase II subunit B) This gene encodes the second largest subunit of RNA polymerase II (Pol II), a DNA-dependent RNA polymerase that catalyzes the transcription of DNA into precursors of mRNA, snRNA and microRNA. This subunit and the largest subunit form opposite sides of the center cleft of Pol II. Deletion of the flap loop region of this subunit results in a decrease in the rate of transcriptional elongation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR2B	NM_000938.3	c.1956-34G>A		intron_variant	Intron 14 of 24	ENST00000314595.6	NP_000929.1
POLR2B	NM_001303269.2	c.1935-34G>A		intron_variant	Intron 15 of 25		NP_001290198.1
POLR2B	NM_001303268.2	c.1731-34G>A		intron_variant	Intron 13 of 23		NP_001290197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR2B	ENST00000314595.6	c.1956-34G>A		intron_variant	Intron 14 of 24	1	NM_000938.3	ENSP00000312735.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1230076 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 616734

African (AFR) AF: 0.00 AC: 0 AN: 28652

American (AMR) AF: 0.00 AC: 0 AN: 36262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22538

East Asian (EAS) AF: 0.00 AC: 0 AN: 35454

South Asian (SAS) AF: 0.00 AC: 0 AN: 65132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5024

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 937718

Other (OTH) AF: 0.00 AC: 0 AN: 50774

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 10368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.87
PhyloP100		-1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1718866; hg19: chr4-57883175;