Variant 17-7445445-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.04

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNB1	NM_000747.3 linkuse as main transcript	c.198+36G>T		intron_variant		ENST00000306071.7	NP_000738.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNB1	ENST00000306071.7 linkuse as main transcript	c.198+36G>T	intron_variant		1	NM_000747.3	ENSP00000304290	P1	P11230-1
CHRNB1	ENST00000570557.5 linkuse as main transcript	c.71+36G>T	intron_variant		5		ENSP00000460648
CHRNB1	ENST00000572857.5 linkuse as main transcript	c.198+36G>T	intron_variant		4		ENSP00000461402
CHRNB1	ENST00000574054.1 linkuse as main transcript	n.254G>T	non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0555

AC:

8380

AN:

150886

Hom.:

760

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0149

AC:

3297

AN:

221490

Hom.:

265

AF XY:

0.0112

AC XY:

1366

AN XY:

122350

show subpopulations

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 SAS exome

AF:

0.00394

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.:

AF XY:

0.00561

AC XY:

4047

AN XY:

721820

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.0123

Gnomad4 ASJ exome

AF:

0.00224

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00374

Gnomad4 FIN exome

AF:

0.0000412

Gnomad4 NFE exome

AF:

0.000536

Gnomad4 OTH exome

AF:

0.0147

GnomAD4 genome

AF:

0.0557

AC:

8416

AN:

151008

Hom.:

766

Cov.:

AF XY:

0.0540

AC XY:

3986

AN XY:

73840

show subpopulations

Gnomad4 AFR

AF:

0.192

Gnomad4 AMR

AF:

0.0219

Gnomad4 ASJ

AF:

0.000578

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00377

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000917

Gnomad4 OTH

AF:

0.0356

Alfa

AF:

0.00475

Hom.:

Bravo

AF:

0.0643

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.0

DANN

Benign

0.56

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over