1-154567996-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000748.3(CHRNB2):c.-49G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000468 in 1,485,118 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (4 hom.)
• Consequence: CHRNB2 NM_000748.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.183

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-154567996-G-C is Benign according to our data. Variant chr1-154567996-G-C is described in ClinVar as [Benign]. Clinvar id is 136771.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00261 (397/152306) while in subpopulation AFR AF= 0.00885 (368/41576). AF 95% confidence interval is 0.00811. There are 2 homozygotes in gnomad4. There are 210 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 396 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNB2	NM_000748.3	c.-49G>C		5_prime_UTR_variant	1/6	ENST00000368476.4
CHRNB2	XR_001736952.3	n.219G>C		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNB2	ENST00000368476.4	c.-49G>C		5_prime_UTR_variant	1/6	1	NM_000748.3	P4
CHRNB2	ENST00000637900.1	c.-49G>C		5_prime_UTR_variant	1/6	5		A1
CHRNB2	ENST00000636034.1	c.-49G>C		5_prime_UTR_variant, NMD_transcript_variant	1/9	5

Frequencies

GnomAD3 genomes AF: 0.00260 AC: 396 AN: 152196 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00885

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000389 AC: 35 AN: 90062 Hom.: 0 AF XY: 0.000352 AC XY: 18 AN XY: 51158

Gnomad AFR exome AF: 0.0153

Gnomad AMR exome AF: 0.000435

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: 0.0000289

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000224 AC: 298 AN: 1332812 Hom.: 4 Cov.: 30 AF XY: 0.000228 AC XY: 150 AN XY: 657228

Gnomad4 AFR exome AF: 0.00803

Gnomad4 AMR exome AF: 0.000543

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000686

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000114

Gnomad4 OTH exome AF: 0.000814

GnomAD4 genome AF: 0.00261 AC: 397 AN: 152306 Hom.: 2 Cov.: 32 AF XY: 0.00282 AC XY: 210 AN XY: 74476

Gnomad4 AFR AF: 0.00885

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000903 Hom.: 0

Bravo AF: 0.00293

Asia WGS AF: 0.000289 AC: 1 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 17, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	11
Dann	Benign	0.63

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: rs551484822; hg19: chr1-154540472;