rs3855924

Variant names:

• chr17-7457004-T-C
• rs3855924
• NM_000747.3:c.*281T>C

Variant summary

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

The NM_000747.3(CHRNB1):​c.*281T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 455,056 control chromosomes in the GnomAD database, including 6,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2209 hom., cov: 32)
  • Exomes 𝑓: 0.17 (4479 hom.)
• Consequence: CHRNB1 NM_000747.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.741
• Publications: 11 publications found

Genes affected

CHRNB1 (HGNC:1961): (cholinergic receptor nicotinic beta 1 subunit) The muscle acetylcholine receptor is composed of five subunits: two alpha subunits and one beta, one gamma, and one delta subunit. This gene encodes the beta subunit of the acetylcholine receptor. The acetylcholine receptor changes conformation upon acetylcholine binding leading to the opening of an ion-conducting channel across the plasma membrane. Mutations in this gene are associated with slow-channel congenital myasthenic syndrome. [provided by RefSeq, Jul 2008]

CHRNB1 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 2C

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, ClinGen
• congenital myasthenic syndrome 1A

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• congenital myasthenic syndrome 2A

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR 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=-0.83).
• BP6: Variant 17-7457004-T-C is Benign according to our data. Variant chr17-7457004-T-C is described in ClinVar as Benign. ClinVar VariationId is 325112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000747.3. 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
	CHRNB1	NM_000747.3	MANE Select	c.*281T>C		3_prime_UTR	Exon 11 of 11	NP_000738.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB1	ENST00000306071.7	TSL:1 MANE Select	c.*281T>C		3_prime_UTR	Exon 11 of 11	ENSP00000304290.2	P11230-1
	CHRNB1	ENST00000576360.1	TSL:3	c.*281T>C		3_prime_UTR	Exon 10 of 10	ENSP00000459092.1	I3L1T7
	CHRNB1	ENST00000575379.1	TSL:2	c.*281T>C		3_prime_UTR	Exon 2 of 2	ENSP00000461751.1	I3L535

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24828 AN: 151992 Hom.: 2198 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.166 AC: 50407 AN: 302944 Hom.: 4479 Cov.: 3 AF XY: 0.168 AC XY: 27096 AN XY: 161652

African (AFR) AF: 0.137 AC: 1216 AN: 8896

American (AMR) AF: 0.208 AC: 2883 AN: 13828

Ashkenazi Jewish (ASJ) AF: 0.0984 AC: 870 AN: 8838

East Asian (EAS) AF: 0.199 AC: 3394 AN: 17030

South Asian (SAS) AF: 0.211 AC: 8683 AN: 41214

European-Finnish (FIN) AF: 0.239 AC: 3869 AN: 16174

Middle Eastern (MID) AF: 0.0795 AC: 97 AN: 1220

European-Non Finnish (NFE) AF: 0.149 AC: 26673 AN: 178794

Other (OTH) AF: 0.161 AC: 2722 AN: 16950

GnomAD4 genome AF: 0.163 AC: 24858 AN: 152112 Hom.: 2209 Cov.: 32 AF XY: 0.169 AC XY: 12576 AN XY: 74346

African (AFR) AF: 0.148 AC: 6132 AN: 41510

American (AMR) AF: 0.197 AC: 3008 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3468

East Asian (EAS) AF: 0.196 AC: 1011 AN: 5168

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4822

European-Finnish (FIN) AF: 0.246 AC: 2597 AN: 10560

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10238 AN: 67982

Other (OTH) AF: 0.160 AC: 338 AN: 2112

Alfa AF: 0.146 Hom.: 2186

Bravo AF: 0.157

Asia WGS AF: 0.269 AC: 934 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital myasthenic syndrome 4C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.31
PhyloP100		0.74
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: rs3855924; hg19: chr17-7360323;