rs10832027

Variant names:

• chr11-13335636-G-A
• rs10832027
• NM_001297719.2:c.-135+9169G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297719.2(BMAL1):​c.-135+9169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,124 control chromosomes in the GnomAD database, including 34,087 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 0.66 (34087 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 37 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297719.2. 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
	BMAL1	NM_001297719.2	MANE Select	c.-135+9169G>A		intron	N/A	NP_001284648.1	O00327-2
	BMAL1	NM_001351807.2		c.-134-14309G>A		intron	N/A	NP_001338736.1
	BMAL1	NM_001351814.2		c.-135+9169G>A		intron	N/A	NP_001338743.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL1	ENST00000403290.6	TSL:1 MANE Select	c.-135+9169G>A		intron	N/A	ENSP00000384517.1	O00327-2
	BMAL1	ENST00000389707.8	TSL:1	c.-135+9169G>A		intron	N/A	ENSP00000374357.4	O00327-8
	BMAL1	ENST00000401424.6	TSL:1	c.-334-14309G>A		intron	N/A	ENSP00000385915.2	O00327-9

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100588 AN: 152006 Hom.: 34035 Cov.: 32

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.667

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.662 AC: 100703 AN: 152124 Hom.: 34087 Cov.: 32 AF XY: 0.651 AC XY: 48434 AN XY: 74354

African (AFR) AF: 0.755 AC: 31314 AN: 41488

American (AMR) AF: 0.613 AC: 9363 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2125 AN: 3466

East Asian (EAS) AF: 0.327 AC: 1693 AN: 5180

South Asian (SAS) AF: 0.549 AC: 2645 AN: 4822

European-Finnish (FIN) AF: 0.529 AC: 5591 AN: 10568

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45959 AN: 68002

Other (OTH) AF: 0.669 AC: 1412 AN: 2112

Alfa AF: 0.672 Hom.: 146375

Bravo AF: 0.675

Asia WGS AF: 0.461 AC: 1607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10832027; hg19: chr11-13357183;