Genetic Variant NM_020183.6:c.*168C>T (chr12-27420700-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_020183.6(BMAL2):c.*168C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 777,024 control chromosomes in the GnomAD database, including 6,726 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 ( 1493 hom., cov: 32)

Exomes 𝑓: 0.13 ( 5233 hom. )

Consequence

BMAL2
NM_020183.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0730

Publications

5 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:

BMAL2-AS1 (HGNC:49892): (BMAL2 antisense RNA 1)

BMAL2-AS1 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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL2	NM_020183.6 link	c.*168C>T		3_prime_UTR_variant	Exon 17 of 17	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.*168C>T		3_prime_UTR_variant	Exon 17 of 17	1	NM_020183.6	ENSP00000266503.5		Q8WYA1-1
BMAL2	ENST00000457040.6 link	c.*168C>T		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000400185.2		H0Y5R1

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

20395

AN:

152062

Hom.:

1472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.0885

Gnomad ASJ

AF:

0.0804

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.125

Gnomad OTH

AF:

0.116

GnomAD4 exome

AF:

0.127

AC:

79180

AN:

624844

Hom.:

5233

Cov.:

AF XY:

0.127

AC XY:

39410

AN XY:

309152

show subpopulations

African (AFR)

AF:

0.183

AC:

2450

AN:

13368

American (AMR)

AF:

0.0676

AC:

761

AN:

11262

Ashkenazi Jewish (ASJ)

AF:

0.0763

AC:

958

AN:

12548

East Asian (EAS)

AF:

0.141

AC:

3575

AN:

25292

South Asian (SAS)

AF:

0.166

AC:

3708

AN:

22394

European-Finnish (FIN)

AF:

0.111

AC:

2990

AN:

26926

Middle Eastern (MID)

AF:

0.144

AC:

316

AN:

2192

European-Non Finnish (NFE)

AF:

0.126

AC:

60613

AN:

480926

Other (OTH)

AF:

0.127

AC:

3809

AN:

29936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3345

6690

10035

13380

16725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1934

3868

5802

7736

9670

<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:

0.134

AC:

20452

AN:

152180

Hom.:

1493

Cov.:

AF XY:

0.133

AC XY:

9895

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.179

AC:

7435

AN:

41494

American (AMR)

AF:

0.0884

AC:

1352

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0804

AC:

279

AN:

3472

East Asian (EAS)

AF:

0.120

AC:

624

AN:

5188

South Asian (SAS)

AF:

0.163

AC:

785

AN:

4826

European-Finnish (FIN)

AF:

0.103

AC:

1086

AN:

10592

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.125

AC:

8473

AN:

67996

Other (OTH)

AF:

0.116

AC:

246

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

916

1832

2747

3663

4579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<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:

0.118

Hom.:

1890

Bravo

AF:

0.132

Asia WGS

AF:

0.152

AC:

529

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.7

(source)

DANN

Benign

0.74

PhyloP100

0.073

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