dbSNP rs2290034: BMAL1:c.1618-52C>T (chr11-13385637-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001297719.2(BMAL1):c.1618-52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,362,966 control chromosomes in the GnomAD database, including 23,457 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 0.19 ( 2863 hom., cov: 32)

Exomes 𝑓: 0.18 ( 20594 hom. )

Consequence

BMAL1
NM_001297719.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33

Publications

8 publications found

Variant links:

Genes affected

BMAL1 (HGNC:701): (basic helix-loop-helix ARNT like 1) The protein encoded by this gene is a basic helix-loop-helix protein that forms a heterodimer with CLOCK. This heterodimer binds E-box enhancer elements upstream of Period (PER1, PER2, PER3) and Cryptochrome (CRY1, CRY2) genes and activates transcription of these genes. PER and CRY proteins heterodimerize and repress their own transcription by interacting in a feedback loop with CLOCK/ARNTL complexes. Defects in this gene have been linked to infertility, problems with gluconeogenesis and lipogenesis, and altered sleep patterns. The protein regulates interferon-stimulated gene expression and is an important factor in viral infection, including COVID-19. [provided by RefSeq, Oct 2021]

BMAL1 links:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2 link	c.1618-52C>T		intron_variant	Intron 18 of 19	ENST00000403290.6	NP_001284648.1	O00327-2B2RCL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6 link	c.1618-52C>T		intron_variant	Intron 18 of 19	1	NM_001297719.2	ENSP00000384517.1		O00327-2

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29168

AN:

152018

Hom.:

2854

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.152

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.185

GnomAD4 exome

AF:

0.179

AC:

216950

AN:

1210830

Hom.:

20594

Cov.:

AF XY:

0.176

AC XY:

107762

AN XY:

610892

show subpopulations

African (AFR)

AF:

0.209

AC:

5896

AN:

28228

American (AMR)

AF:

0.319

AC:

13260

AN:

41600

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

2521

AN:

24068

East Asian (EAS)

AF:

0.191

AC:

7259

AN:

38084

South Asian (SAS)

AF:

0.127

AC:

10108

AN:

79398

European-Finnish (FIN)

AF:

0.213

AC:

11135

AN:

52378

Middle Eastern (MID)

AF:

0.0901

AC:

467

AN:

5182

European-Non Finnish (NFE)

AF:

0.177

AC:

157380

AN:

890154

Other (OTH)

AF:

0.172

AC:

8924

AN:

51738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

8366

16732

25099

33465

41831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5244

10488

15732

20976

26220

<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:

0.192

AC:

29212

AN:

152136

Hom.:

2863

Cov.:

AF XY:

0.193

AC XY:

14324

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.212

AC:

8816

AN:

41488

American (AMR)

AF:

0.254

AC:

3883

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

359

AN:

3466

East Asian (EAS)

AF:

0.169

AC:

873

AN:

5170

South Asian (SAS)

AF:

0.127

AC:

612

AN:

4818

European-Finnish (FIN)

AF:

0.219

AC:

2315

AN:

10586

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.173

AC:

11793

AN:

67998

Other (OTH)

AF:

0.182

AC:

385

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1198

2396

3594

4792

5990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.173

Hom.:

1550

Bravo

AF:

0.198

Asia WGS

AF:

0.145

AC:

503

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.2

(source)

DANN

Benign

0.40

PhyloP100

-1.3

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

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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