chr17-7445445-G-T

Variant names:

• chr17-7445445-G-T
• rs60038135
• NM_000747.3:c.198+36G>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.198+36G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,602,686 control chromosomes in the GnomAD database, including 1,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (766 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (755 hom.)
• Consequence: CHRNB1 NM_000747.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.04
• Publications: 2 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

ENSG00000272884 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-7445445-G-T is Benign according to our data. Variant chr17-7445445-G-T is described in ClinVar as Benign. ClinVar VariationId is 256774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 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.198+36G>T		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.198+36G>T		intron	N/A	ENSP00000304290.2
	ENSG00000272884	ENST00000575331.1	TSL:1	n.5032G>T		non_coding_transcript_exon	Exon 3 of 3
	CHRNB1	ENST00000570557.5	TSL:5	c.69+36G>T		intron	N/A	ENSP00000460648.1

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8380 AN: 150886 Hom.: 760 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.000578

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00398

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0199

Gnomad NFE AF: 0.000917

Gnomad OTH AF: 0.0360

GnomAD2 exomes AF: 0.0149 AC: 3297 AN: 221490 AF XY: 0.0112

Gnomad AFR exome AF: 0.208

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.00225

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000931

Gnomad OTH exome AF: 0.00871

GnomAD4 exome AF: 0.00644 AC: 9343 AN: 1451678 Hom.: 755 Cov.: 34 AF XY: 0.00561 AC XY: 4047 AN XY: 721820

African (AFR) AF: 0.206 AC: 6872 AN: 33414

American (AMR) AF: 0.0123 AC: 542 AN: 43932

Ashkenazi Jewish (ASJ) AF: 0.00224 AC: 58 AN: 25912

East Asian (EAS) AF: 0.00 AC: 0 AN: 39594

South Asian (SAS) AF: 0.00374 AC: 319 AN: 85354

European-Finnish (FIN) AF: 0.0000412 AC: 2 AN: 48508

Middle Eastern (MID) AF: 0.0125 AC: 72 AN: 5754

European-Non Finnish (NFE) AF: 0.000536 AC: 595 AN: 1109176

Other (OTH) AF: 0.0147 AC: 883 AN: 60034

GnomAD4 genome AF: 0.0557 AC: 8416 AN: 151008 Hom.: 766 Cov.: 32 AF XY: 0.0540 AC XY: 3986 AN XY: 73840

African (AFR) AF: 0.192 AC: 7922 AN: 41188

American (AMR) AF: 0.0219 AC: 333 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.000578 AC: 2 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 4962

South Asian (SAS) AF: 0.00377 AC: 18 AN: 4772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

Middle Eastern (MID) AF: 0.0177 AC: 5 AN: 282

European-Non Finnish (NFE) AF: 0.000917 AC: 62 AN: 67586

Other (OTH) AF: 0.0356 AC: 74 AN: 2078

Alfa AF: 0.00475 Hom.: 3

Bravo AF: 0.0643

Asia WGS AF: 0.0170 AC: 61 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	-0.81
CADD	Benign	1.0
DANN	Benign	0.56
PhyloP100		-1.0
PromoterAI		-0.079	Neutral
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: rs60038135; hg19: chr17-7348764;