8-42731962-T-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000749.5(CHRNB3):āc.655T>Cā(p.Ser219Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,614,082 control chromosomes in the GnomAD database, including 2 homozygotes. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S219A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000749.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNB3 | NM_000749.5 | c.655T>C | p.Ser219Pro | missense_variant | 5/6 | ENST00000289957.3 | |
CHRNB3 | NM_001347717.2 | c.433T>C | p.Ser145Pro | missense_variant | 6/7 | ||
CHRNB3 | XM_011544390.3 | c.268T>C | p.Ser90Pro | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNB3 | ENST00000289957.3 | c.655T>C | p.Ser219Pro | missense_variant | 5/6 | 1 | NM_000749.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152112Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251422Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135874
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461852Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 727226
GnomAD4 genome AF: 0.000112 AC: 17AN: 152230Hom.: 2 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74446
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 27, 2023 | The c.655T>C (p.S219P) alteration is located in exon 5 (coding exon 5) of the CHRNB3 gene. This alteration results from a T to C substitution at nucleotide position 655, causing the serine (S) at amino acid position 219 to be replaced by a proline (P). 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