rs281865072

chr1-154571833-T-Achr1-154571833-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000748.3(CHRNB2):c.1010T>A(p.Val337Asp) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V337I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHRNB2 NM_000748.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

Genes affected

CHRNB2 (HGNC:1962): (cholinergic receptor nicotinic beta 2 subunit) Neuronal acetylcholine receptors are homo- or heteropentameric complexes composed of homologous alpha and beta subunits. They belong to a superfamily of ligand-gated ion channels which allow the flow of sodium and potassium across the plasma membrane in response to ligands such as acetylcholine and nicotine. This gene encodes one of several beta subunits. Mutations in this gene are associated with autosomal dominant nocturnal frontal lobe epilepsy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14771953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNB2	NM_000748.3	c.1010T>A	p.Val337Asp	missense_variant	5/6	ENST00000368476.4
CHRNB2	XM_017000180.3	c.500T>A	p.Val167Asp	missense_variant	2/3
CHRNB2	XR_001736952.3	n.1277T>A		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNB2	ENST00000368476.4	c.1010T>A	p.Val337Asp	missense_variant	5/6	1	NM_000748.3	P4
CHRNB2	ENST00000637900.1	c.1016T>A	p.Val339Asp	missense_variant	5/6	5		A1
CHRNB2	ENST00000636034.1	c.1010T>A	p.Val337Asp	missense_variant, NMD_transcript_variant	5/9	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248322 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134524

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1460862 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726782

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
Cadd	Benign	16
Dann	Benign	0.81
DEOGEN2	Uncertain	0.50	D;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.085	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.7	M;.
MutationTaster	Benign	0.84	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.68	N;.
REVEL	Uncertain	0.51
Sift	Benign	0.26	T;.
Sift4G	Benign	0.14	T;.
Polyphen		0.31	B;.
Vest4		0.58
MutPred		0.52		Loss of ubiquitination at K342 (P = 0.1668);.;
MVP		0.94
MPC		1.9
ClinPred		0.057	T
GERP RS		1.6
Varity_R		0.44
gMVP		0.92

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

Publications

LitVar

Other links and lift over

dbSNP: rs281865072; hg19: chr1-154544309;