chr15-78625057-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001256567.3(CHRNB4):c.594T>C(p.Ala198Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,609,104 control chromosomes in the GnomAD database, including 361,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A198A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.70 ( 37855 hom., cov: 33)

Exomes 𝑓: 0.66 ( 323365 hom. )

Consequence

CHRNB4
NM_001256567.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.921

Publications

91 publications found

Variant links:

Genes affected

CHRNB4 (HGNC:1964): (cholinergic receptor nicotinic beta 4 subunit) This gene is found within a conserved gene cluster and encodes one of the beta subunits of the nicotinic acetylcholine receptor (nAChRs) superfamily which form ligand-gated ion channels with a central pore that forms a cation channel. Neuronal nAChRs are pentameric structures that can be either homomeric or heteromeric, with heteromeric structures containing both alpha and beta subunits. Each subunit contains an extracellular amino terminus and four transmembrane domains. Nicotine is one of the agonists that binds to the receptor. Variants in this gene have been associated with nicotine dependence and lung cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2017]

CHRNB4 Gene-Disease associations (from GenCC):

lung cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CHRNB4 links:

ENSG00000259555 (HGNC:):

ENSG00000259555 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001256567.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-78625057-A-G is Benign according to our data. Variant chr15-78625057-A-G is described in ClinVar as Benign. ClinVar VariationId is 1289303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.921 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256567.3. 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
	CHRNB4	NM_000750.5	MANE Select	c.*76T>C		3_prime_UTR	Exon 6 of 6	NP_000741.1	P30926-1
	CHRNB4	NM_001256567.3		c.594T>C	p.Ala198Ala	synonymous	Exon 5 of 5	NP_001243496.1	P30926-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHRNB4	ENST00000412074.6	TSL:1	c.594T>C	p.Ala198Ala	synonymous	Exon 5 of 5	ENSP00000416386.2	P30926-2
CHRNB4	ENST00000261751.8	TSL:1 MANE Select	c.*76T>C		3_prime_UTR	Exon 6 of 6	ENSP00000261751.3	P30926-1
CHRNB4	ENST00000929174.1		c.*76T>C		3_prime_UTR	Exon 7 of 7	ENSP00000599233.1

Frequencies

GnomAD3 genomes

AF:

0.702

AC:

106744

AN:

151950

Hom.:

37800

Cov.:

show subpopulations

Gnomad AFR

AF:

0.778

Gnomad AMI

AF:

0.627

Gnomad AMR

AF:

0.786

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.685

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.706

GnomAD2 exomes

AF:

0.694

AC:

169878

AN:

244840

AF XY:

0.689

show subpopulations

Gnomad AFR exome

AF:

0.782

Gnomad AMR exome

AF:

0.861

Gnomad ASJ exome

AF:

0.686

Gnomad EAS exome

AF:

0.523

Gnomad FIN exome

AF:

0.671

Gnomad NFE exome

AF:

0.659

Gnomad OTH exome

AF:

0.686

GnomAD4 exome

AF:

0.664

AC:

967529

AN:

1457036

Hom.:

323365

Cov.:

AF XY:

0.664

AC XY:

481318

AN XY:

724976

show subpopulations

African (AFR)

AF:

0.782

AC:

26177

AN:

33478

American (AMR)

AF:

0.851

AC:

38072

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.675

AC:

17651

AN:

26132

East Asian (EAS)

AF:

0.558

AC:

22137

AN:

39690

South Asian (SAS)

AF:

0.697

AC:

60108

AN:

86240

European-Finnish (FIN)

AF:

0.669

AC:

32717

AN:

48918

Middle Eastern (MID)

AF:

0.723

AC:

4165

AN:

5764

European-Non Finnish (NFE)

AF:

0.653

AC:

726401

AN:

1111760

Other (OTH)

AF:

0.665

AC:

40101

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

18563

37127

55690

74254

92817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19052

38104

57156

76208

95260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.703

AC:

106854

AN:

152068

Hom.:

37855

Cov.:

AF XY:

0.703

AC XY:

52240

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.778

AC:

32274

AN:

41488

American (AMR)

AF:

0.786

AC:

12025

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.672

AC:

2329

AN:

3464

East Asian (EAS)

AF:

0.529

AC:

2738

AN:

5172

South Asian (SAS)

AF:

0.686

AC:

3313

AN:

4826

European-Finnish (FIN)

AF:

0.670

AC:

7070

AN:

10558

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.659

AC:

44804

AN:

67950

Other (OTH)

AF:

0.711

AC:

1501

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1691

3382

5073

6764

8455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

822

1644

2466

3288

4110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.675

Hom.:

57366

Bravo

AF:

0.714

Asia WGS

AF:

0.654

AC:

2278

AN:

3478

EpiCase

AF:

0.675

EpiControl

AF:

0.669

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.98

(source)

DANN

Benign

0.46

PhyloP100

-0.92

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over