rs4845378

Variant names:

• chr1-154572175-G-T
• rs4845378
• NM_000748.3:c.1338+14G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-154572175-G-T
• chr1-154572175-G-A

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.1338+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 1,536,424 control chromosomes in the GnomAD database, including 6,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (563 hom., cov: 32)
  • Exomes 𝑓: 0.087 (5534 hom.)
• Consequence: CHRNB2 NM_000748.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.531
• Publications: 22 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-154572175-G-T is Benign according to our data. Variant chr1-154572175-G-T is described in ClinVar as Benign. ClinVar VariationId is 158331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000748.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB2	NM_000748.3	MANE Select	c.1338+14G>T		intron	N/A	NP_000739.1	P17787

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB2	ENST00000368476.4	TSL:1 MANE Select	c.1338+14G>T		intron	N/A	ENSP00000357461.3	P17787
	CHRNB2	ENST00000637900.1	TSL:5	c.1344+14G>T		intron	N/A	ENSP00000490474.1	A0A1B0GVD7
	CHRNB2	ENST00000636034.1	TSL:5	n.1338+14G>T		intron	N/A	ENSP00000489703.1	A0A1B0GTH5

Frequencies

GnomAD3 genomes AF: 0.0808 AC: 12285 AN: 152122 Hom.: 568 Cov.: 32

Gnomad AFR AF: 0.0563

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0837

Gnomad OTH AF: 0.0941

GnomAD2 exomes AF: 0.0989 AC: 13032 AN: 131748 AF XY: 0.101

Gnomad AFR exome AF: 0.0567

Gnomad AMR exome AF: 0.0932

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.143

Gnomad FIN exome AF: 0.0542

Gnomad NFE exome AF: 0.0853

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.0865 AC: 119776 AN: 1384182 Hom.: 5534 Cov.: 34 AF XY: 0.0881 AC XY: 60206 AN XY: 683138

African (AFR) AF: 0.0564 AC: 1779 AN: 31516

American (AMR) AF: 0.0939 AC: 3352 AN: 35682

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2850 AN: 25164

East Asian (EAS) AF: 0.118 AC: 4209 AN: 35718

South Asian (SAS) AF: 0.137 AC: 10882 AN: 79160

European-Finnish (FIN) AF: 0.0518 AC: 1874 AN: 36152

Middle Eastern (MID) AF: 0.145 AC: 644 AN: 4446

European-Non Finnish (NFE) AF: 0.0824 AC: 88854 AN: 1078606

Other (OTH) AF: 0.0923 AC: 5332 AN: 57738

GnomAD4 genome AF: 0.0807 AC: 12283 AN: 152242 Hom.: 563 Cov.: 32 AF XY: 0.0806 AC XY: 6002 AN XY: 74444

African (AFR) AF: 0.0563 AC: 2339 AN: 41556

American (AMR) AF: 0.0984 AC: 1505 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 470 AN: 3468

East Asian (EAS) AF: 0.129 AC: 668 AN: 5180

South Asian (SAS) AF: 0.149 AC: 719 AN: 4832

European-Finnish (FIN) AF: 0.0555 AC: 588 AN: 10602

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0837 AC: 5689 AN: 67990

Other (OTH) AF: 0.0945 AC: 200 AN: 2116

Alfa AF: 0.0835 Hom.: 103

Bravo AF: 0.0815

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Autosomal dominant nocturnal frontal lobe epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.73
PhyloP100		0.53
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs4845378; hg19: chr1-154544651; COSMIC: COSV63809549; COSMIC: COSV63809549;