rs17856697

Variant names:

• chr17-7445306-A-G
• rs17856697
• NM_000747.3:c.95A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-7445306-A-G
• chr17-7445306-A-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.95A>G​(p.Glu32Gly) variant causes a missense change. The variant allele was found at a frequency of 0.319 in 1,612,188 control chromosomes in the GnomAD database, including 91,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E32V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.24 (6030 hom., cov: 32)
  • Exomes 𝑓: 0.33 (85718 hom.)
• Consequence: CHRNB1 NM_000747.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 6.06
• Publications: 27 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: AR, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Ambry Genetics
• congenital myasthenic syndrome 2A

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000272884 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031630695).
• BP6: Variant 17-7445306-A-G is Benign according to our data. Variant chr17-7445306-A-G is described in ClinVar as Benign. ClinVar VariationId is 128754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 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.95A>G	p.Glu32Gly	missense	Exon 2 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.95A>G	p.Glu32Gly	missense	Exon 2 of 11	ENSP00000304290.2	P11230-1
	ENSG00000272884	ENST00000575331.1	TSL:1	n.4893A>G		non_coding_transcript_exon	Exon 3 of 3
	CHRNB1	ENST00000572857.5	TSL:4	c.95A>G	p.Glu32Gly	missense	Exon 2 of 6	ENSP00000461402.1	I3L4N5

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36844 AN: 151998 Hom.: 6033 Cov.: 32

Gnomad AFR AF: 0.0631

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.282

GnomAD2 exomes AF: 0.248 AC: 60334 AN: 243398 AF XY: 0.254

Gnomad AFR exome AF: 0.0517

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.000658

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.364

Gnomad OTH exome AF: 0.291

GnomAD4 exome AF: 0.327 AC: 478142 AN: 1460072 Hom.: 85718 Cov.: 52 AF XY: 0.323 AC XY: 234714 AN XY: 726302

African (AFR) AF: 0.0523 AC: 1749 AN: 33464

American (AMR) AF: 0.171 AC: 7638 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 9318 AN: 26110

East Asian (EAS) AF: 0.000655 AC: 26 AN: 39678

South Asian (SAS) AF: 0.121 AC: 10433 AN: 86198

European-Finnish (FIN) AF: 0.278 AC: 14608 AN: 52548

Middle Eastern (MID) AF: 0.321 AC: 1853 AN: 5768

European-Non Finnish (NFE) AF: 0.373 AC: 414317 AN: 1111426

Other (OTH) AF: 0.302 AC: 18200 AN: 60250

GnomAD4 genome AF: 0.242 AC: 36826 AN: 152116 Hom.: 6030 Cov.: 32 AF XY: 0.234 AC XY: 17413 AN XY: 74380

African (AFR) AF: 0.0630 AC: 2613 AN: 41506

American (AMR) AF: 0.233 AC: 3561 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3472

East Asian (EAS) AF: 0.00252 AC: 13 AN: 5162

South Asian (SAS) AF: 0.112 AC: 539 AN: 4824

European-Finnish (FIN) AF: 0.275 AC: 2911 AN: 10590

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24907 AN: 67956

Other (OTH) AF: 0.279 AC: 588 AN: 2110

Alfa AF: 0.332 Hom.: 14866

Bravo AF: 0.231

TwinsUK AF: 0.379 AC: 1404

ALSPAC AF: 0.369 AC: 1422

ESP6500AA AF: 0.0641 AC: 282

ESP6500EA AF: 0.354 AC: 3042

ExAC AF: 0.244 AC: 29534

Asia WGS AF: 0.0540 AC: 186 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.95	D
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		6.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.32
Sift	Benign	0.26	T
Sift4G	Benign	0.18	T
Polyphen		0.77	P
Vest4		0.11
MPC		0.70
ClinPred		0.037	T
GERP RS		5.4
PromoterAI		0.037	Neutral
Varity_R		0.24
gMVP		0.53
Mutation Taster		=88/12	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17856697; hg19: chr17-7348625; COSMIC: COSV53439803; COSMIC: COSV53439803;