4-56990876-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_000938.3(POLR2B):c.221C>T(p.Ala74Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000931 in 1,612,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000938.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLR2B | NM_000938.3 | c.221C>T | p.Ala74Val | missense_variant | 3/25 | ENST00000314595.6 | NP_000929.1 | |
POLR2B | NM_001303269.2 | c.200C>T | p.Ala67Val | missense_variant | 4/26 | NP_001290198.1 | ||
POLR2B | NM_001303268.2 | c.19-3528C>T | intron_variant | NP_001290197.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249130Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134676
GnomAD4 exome AF: 0.00000480 AC: 7AN: 1459748Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4AN XY: 726134
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152284Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74460
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2023 | The c.221C>T (p.A74V) alteration is located in exon 3 (coding exon 3) of the POLR2B gene. This alteration results from a C to T substitution at nucleotide position 221, causing the alanine (A) at amino acid position 74 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at