1-154568006-C-G

Variant names:

• chr1-154568006-C-G
• rs761649443
• NM_000748.3:c.-39C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000748.3(CHRNB2):​c.-39C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000544 in 1,508,214 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000052 (0 hom.)
• Consequence: CHRNB2 NM_000748.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.39
• Publications: 0 publications found

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]

CHRNB2 Gene-Disease associations (from GenCC):

• familial sleep-related hypermotor epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant nocturnal frontal lobe epilepsy 3

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal dominant nocturnal frontal lobe epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286391 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-154568006-C-G is Benign according to our data. Variant chr1-154568006-C-G is described in ClinVar as [Benign]. Clinvar id is 1182200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNB2	NM_000748.3	c.-39C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	ENST00000368476.4	NP_000739.1
CHRNB2	NM_000748.3	c.-39C>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000368476.4	NP_000739.1
CHRNB2	XR_001736952.3	n.229C>G		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.-39C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	1	NM_000748.3	ENSP00000357461.3
CHRNB2	ENST00000368476.4	c.-39C>G		5_prime_UTR_variant	Exon 1 of 6	1	NM_000748.3	ENSP00000357461.3

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152210 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000919 AC: 10 AN: 108846 AF XY: 0.0000654

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000255

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000119

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000516 AC: 70 AN: 1356004 Hom.: 0 Cov.: 30 AF XY: 0.0000553 AC XY: 37 AN XY: 669340

African (AFR) AF: 0.00 AC: 0 AN: 28128

American (AMR) AF: 0.000383 AC: 12 AN: 31310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23894

East Asian (EAS) AF: 0.00 AC: 0 AN: 31890

South Asian (SAS) AF: 0.00 AC: 0 AN: 75526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39094

Middle Eastern (MID) AF: 0.000207 AC: 1 AN: 4820

European-Non Finnish (NFE) AF: 0.0000507 AC: 54 AN: 1065132

Other (OTH) AF: 0.0000534 AC: 3 AN: 56210

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152210 Hom.: 1 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.000523 AC: 8 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000869

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 22, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.54
PhyloP100		-2.4
PromoterAI		0.038	Neutral
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs761649443; hg19: chr1-154540482;