rs7210231

Variant names:

• chr17-7454545-C-A
• rs7210231
• NM_000747.3:c.1044+25C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7454545-C-A
• chr17-7454545-C-G
• chr17-7454545-C-T

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.1044+25C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,587,778 control chromosomes in the GnomAD database, including 35,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3186 hom., cov: 30)
  • Exomes 𝑓: 0.21 (31960 hom.)
• Consequence: CHRNB1 NM_000747.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.20
• Publications: 15 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, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• congenital myasthenic syndrome 1A

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

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000308645 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 17-7454545-C-A is Benign according to our data. Variant chr17-7454545-C-A is described in ClinVar as Benign. ClinVar VariationId is 256771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 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.1044+25C>A		intron	N/A	NP_000738.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNB1	ENST00000306071.7	TSL:1 MANE Select	c.1044+25C>A		intron	N/A	ENSP00000304290.2
	CHRNB1	ENST00000536404.6	TSL:2	c.828+25C>A		intron	N/A	ENSP00000439209.2
	CHRNB1	ENST00000576360.1	TSL:3	c.681+25C>A		intron	N/A	ENSP00000459092.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30186 AN: 151950 Hom.: 3191 Cov.: 30

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.211

GnomAD2 exomes AF: 0.192 AC: 48042 AN: 250578 AF XY: 0.200

Gnomad AFR exome AF: 0.220

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.0401

Gnomad FIN exome AF: 0.178

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.206 AC: 295078 AN: 1435710 Hom.: 31960 Cov.: 27 AF XY: 0.208 AC XY: 148654 AN XY: 715810

African (AFR) AF: 0.217 AC: 7144 AN: 32918

American (AMR) AF: 0.118 AC: 5278 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 5926 AN: 25990

East Asian (EAS) AF: 0.0529 AC: 2093 AN: 39582

South Asian (SAS) AF: 0.273 AC: 23395 AN: 85736

European-Finnish (FIN) AF: 0.181 AC: 9639 AN: 53394

Middle Eastern (MID) AF: 0.277 AC: 1555 AN: 5616

European-Non Finnish (NFE) AF: 0.209 AC: 227826 AN: 1088348

Other (OTH) AF: 0.206 AC: 12222 AN: 59472

GnomAD4 genome AF: 0.199 AC: 30189 AN: 152068 Hom.: 3186 Cov.: 30 AF XY: 0.196 AC XY: 14584 AN XY: 74340

African (AFR) AF: 0.218 AC: 9052 AN: 41450

American (AMR) AF: 0.153 AC: 2344 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3470

East Asian (EAS) AF: 0.0361 AC: 187 AN: 5182

South Asian (SAS) AF: 0.278 AC: 1341 AN: 4828

European-Finnish (FIN) AF: 0.168 AC: 1781 AN: 10576

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13929 AN: 67960

Other (OTH) AF: 0.208 AC: 440 AN: 2112

Alfa AF: 0.163 Hom.: 540

Bravo AF: 0.198

Asia WGS AF: 0.148 AC: 516 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	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.4
DANN	Benign	0.78
PhyloP100		1.2
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: rs7210231; hg19: chr17-7357864; COSMIC: COSV60140501; COSMIC: COSV60140501;