rs11824092

Variant names:

• chr11-13324747-T-C
• rs11824092
• NM_001297719.2:c.-189-1666T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-13324747-T-C
• chr11-13324747-T-G

Variant summary

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

The NM_001297719.2(BMAL1):​c.-189-1666T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,110 control chromosomes in the GnomAD database, including 28,862 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 0.61 (28862 hom., cov: 33)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973
• Publications: 13 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-189-1666T>C		intron_variant	Intron 2 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.-189-1666T>C		intron_variant	Intron 2 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93195 AN: 151992 Hom.: 28830 Cov.: 33

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.613 AC: 93281 AN: 152110 Hom.: 28862 Cov.: 33 AF XY: 0.605 AC XY: 44999 AN XY: 74326

African (AFR) AF: 0.665 AC: 27599 AN: 41480

American (AMR) AF: 0.606 AC: 9258 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2081 AN: 3470

East Asian (EAS) AF: 0.406 AC: 2102 AN: 5174

South Asian (SAS) AF: 0.492 AC: 2376 AN: 4826

European-Finnish (FIN) AF: 0.524 AC: 5529 AN: 10556

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42422 AN: 68008

Other (OTH) AF: 0.648 AC: 1365 AN: 2106

Alfa AF: 0.609 Hom.: 8031

Bravo AF: 0.626

Asia WGS AF: 0.483 AC: 1679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.69
DANN	Benign	0.55
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11824092; hg19: chr11-13346294;