Genetic Variant ENSG00000290083:n.478A>G (chr11-13276938-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000702886.2(ENSG00000290083):n.478A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,194 control chromosomes in the GnomAD database, including 30,125 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 0.62 ( 30122 hom., cov: 35)

Exomes 𝑓: 0.80 ( 3 hom. )

Consequence

ENSG00000290083
ENST00000702886.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.811

Publications

37 publications found

Variant links:

Genes affected

ENSG00000290083 (HGNC:):

ENSG00000290083 links:

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 (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
BMAL1	NM_001351804.1 link	c.-397T>C	5_prime_UTR_variant	Exon 1 of 20	NP_001338733.1
BMAL1	XM_017017738.3 link	c.-87T>C	5_prime_UTR_variant	Exon 1 of 18	XP_016873227.1
BMAL1	XM_011520105.4 link	c.-87T>C	5_prime_UTR_variant	Exon 1 of 18	XP_011518407.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
ENSG00000290083	ENST00000702886.2 link	n.478A>G	non_coding_transcript_exon_variant	Exon 1 of 1
BMAL1	ENST00000534544.5 link	c.-342T>C	5_prime_UTR_variant	Exon 1 of 5	5	ENSP00000431566.1
BMAL1	ENST00000529050.5 link	c.-216T>C	5_prime_UTR_variant	Exon 1 of 3	4	ENSP00000434044.1

Frequencies

GnomAD3 genomes

AF:

0.620

AC:

94238

AN:

152066

Hom.:

30089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.463

Gnomad AMI

AF:

0.610

Gnomad AMR

AF:

0.618

Gnomad ASJ

AF:

0.661

Gnomad EAS

AF:

0.536

Gnomad SAS

AF:

0.635

Gnomad FIN

AF:

0.723

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.702

Gnomad OTH

AF:

0.637

GnomAD4 exome

AF:

0.800

AC:

AN:

Hom.:

Cov.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.833

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.620

AC:

94324

AN:

152184

Hom.:

30122

Cov.:

AF XY:

0.622

AC XY:

46298

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.463

AC:

19211

AN:

41498

American (AMR)

AF:

0.618

AC:

9456

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.661

AC:

2295

AN:

3470

East Asian (EAS)

AF:

0.535

AC:

2770

AN:

5174

South Asian (SAS)

AF:

0.638

AC:

3078

AN:

4822

European-Finnish (FIN)

AF:

0.723

AC:

7659

AN:

10592

Middle Eastern (MID)

AF:

0.596

AC:

174

AN:

292

European-Non Finnish (NFE)

AF:

0.702

AC:

47775

AN:

68012

Other (OTH)

AF:

0.640

AC:

1351

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1856

3712

5569

7425

9281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.650

Hom.:

13339

Bravo

AF:

0.607

Asia WGS

AF:

0.604

AC:

2100

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

5.7

(source)

DANN

Benign

0.40

PhyloP100

-0.81

PromoterAI

0.037

Neutral

(source)

Splicing

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