chr8-42732431-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000749.5(CHRNB3):c.1124A>G(p.Lys375Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,614,146 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000749.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNB3 | NM_000749.5 | c.1124A>G | p.Lys375Arg | missense_variant | 5/6 | ENST00000289957.3 | |
CHRNB3 | NM_001347717.2 | c.902A>G | p.Lys301Arg | missense_variant | 6/7 | ||
CHRNB3 | XM_011544390.3 | c.737A>G | p.Lys246Arg | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNB3 | ENST00000289957.3 | c.1124A>G | p.Lys375Arg | missense_variant | 5/6 | 1 | NM_000749.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152186Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 251014Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135714
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461842Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727224
GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152304Hom.: 1 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74474
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 06, 2021 | The c.1124A>G (p.K375R) alteration is located in exon 5 (coding exon 5) of the CHRNB3 gene. This alteration results from a A to G substitution at nucleotide position 1124, causing the lysine (K) at amino acid position 375 to be replaced by an arginine (R). 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