1-154567990-C-T

Variant names:

• chr1-154567990-C-T
• rs55799808
• NM_000748.3:c.-55C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000748.3(CHRNB2):​c.-55C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,470,084 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (143 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (89 hom.)
• Consequence: CHRNB2 NM_000748.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.202

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]

ENSG00000286391 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-154567990-C-T is Benign according to our data. Variant chr1-154567990-C-T is described in ClinVar as [Benign]. Clinvar id is 670849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB2	NM_000748.3	c.-55C>T		5_prime_UTR_variant	Exon 1 of 6	ENST00000368476.4	NP_000739.1
CHRNB2	XR_001736952.3	n.213C>T		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNB2	ENST00000368476.4	c.-55C>T		5_prime_UTR_variant	Exon 1 of 6	1	NM_000748.3	ENSP00000357461.3

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3401 AN: 152174 Hom.: 142 Cov.: 32

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.00199 AC: 2617 AN: 1317802 Hom.: 89 Cov.: 27 AF XY: 0.00166 AC XY: 1077 AN XY: 649358

African (AFR) AF: 0.0828 AC: 2222 AN: 26836

American (AMR) AF: 0.00354 AC: 92 AN: 25982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22208

East Asian (EAS) AF: 0.0000326 AC: 1 AN: 30670

South Asian (SAS) AF: 0.000282 AC: 20 AN: 70962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35620

Middle Eastern (MID) AF: 0.00322 AC: 14 AN: 4344

European-Non Finnish (NFE) AF: 0.0000287 AC: 30 AN: 1046502

Other (OTH) AF: 0.00435 AC: 238 AN: 54678

GnomAD4 genome AF: 0.0224 AC: 3410 AN: 152282 Hom.: 143 Cov.: 32 AF XY: 0.0207 AC XY: 1538 AN XY: 74456

African (AFR) AF: 0.0793 AC: 3298 AN: 41564

American (AMR) AF: 0.00529 AC: 81 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68006

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.0192 Hom.: 19

Bravo AF: 0.0242

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.75
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		0.20
PromoterAI		-0.12	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

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Other links and lift over

dbSNP: rs55799808; hg19: chr1-154540466;