dbSNP rs17413842: BMAL2:c.183-139G>A (chr12-27369990-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020183.6(BMAL2):c.183-139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 633,974 control chromosomes in the GnomAD database, including 6,792 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1390 hom., cov: 32)

Exomes 𝑓: 0.14 ( 5402 hom. )

Consequence

BMAL2
NM_020183.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.405

Publications

3 publications found

Variant links:

Genes affected

BMAL2 (HGNC:18984): (basic helix-loop-helix ARNT like 2) This gene encodes a basic helix-loop-helix transcription factor belonging to the PAS (PER, ARNT, SIM) superfamily. The PAS proteins play important roles in adaptation to low atmospheric and cellular oxygen levels, exposure to certain environmental pollutants, and diurnal oscillations in light and temperature. This protein forms a transcriptionally active heterodimer with the circadian CLOCK protein, the structurally related MOP4, and hypoxia-inducible factors, such as HIF1alpha. Consistent with its role as a biologically relevant partner of circadian and hypoxia factors, this protein is coexpressed in regions of the brain such as the thalamus, hypothalamus, and amygdala. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

BMAL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL2	NM_020183.6 link	c.183-139G>A		intron_variant	Intron 2 of 16	ENST00000266503.10	NP_064568.3	Q8WYA1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL2	ENST00000266503.10 link	c.183-139G>A		intron_variant	Intron 2 of 16	1	NM_020183.6	ENSP00000266503.5		Q8WYA1-1
BMAL2	ENST00000457040.6 link	c.117-178G>A		intron_variant	Intron 1 of 14	1		ENSP00000400185.2		H0Y5R1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19136

AN:

151972

Hom.:

1388

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0632

Gnomad AMI

AF:

0.0626

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.0625

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.129

GnomAD4 exome

AF:

0.143

AC:

68751

AN:

481884

Hom.:

5402

AF XY:

0.143

AC XY:

36700

AN XY:

256862

show subpopulations

African (AFR)

AF:

0.0642

AC:

888

AN:

13828

American (AMR)

AF:

0.0879

AC:

2193

AN:

24944

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

1377

AN:

13640

East Asian (EAS)

AF:

0.0579

AC:

1927

AN:

33300

South Asian (SAS)

AF:

0.127

AC:

5895

AN:

46504

European-Finnish (FIN)

AF:

0.162

AC:

6133

AN:

37868

Middle Eastern (MID)

AF:

0.0802

AC:

164

AN:

2044

European-Non Finnish (NFE)

AF:

0.165

AC:

46593

AN:

283056

Other (OTH)

AF:

0.134

AC:

3581

AN:

26700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2669

5338

8008

10677

13346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.126

AC:

19146

AN:

152090

Hom.:

1390

Cov.:

AF XY:

0.125

AC XY:

9260

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0633

AC:

2628

AN:

41508

American (AMR)

AF:

0.0999

AC:

1526

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

362

AN:

3466

East Asian (EAS)

AF:

0.0625

AC:

324

AN:

5186

South Asian (SAS)

AF:

0.127

AC:

613

AN:

4816

European-Finnish (FIN)

AF:

0.169

AC:

1784

AN:

10576

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.170

AC:

11564

AN:

67948

Other (OTH)

AF:

0.129

AC:

273

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

838

1676

2513

3351

4189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<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:

0.141

Hom.:

293

Bravo

AF:

0.116

Asia WGS

AF:

0.113

AC:

397

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.95

(source)

DANN

Benign

0.64

PhyloP100

-0.41

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over