rs10832020

Variant names:

• chr11-13299796-T-C
• rs10832020
• NM_001297719.2:c.-262-10191T>C

Variant summary

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

The NM_001297719.2(BMAL1):​c.-262-10191T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,152 control chromosomes in the GnomAD database, including 1,678 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 0.14 (1678 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 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.-262-10191T>C		intron	N/A	NP_001284648.1	O00327-2
	BMAL1	NM_001351807.2		c.-207-10191T>C		intron	N/A	NP_001338736.1
	BMAL1	NM_001351814.2		c.-262-10191T>C		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.-262-10191T>C		intron	N/A	ENSP00000384517.1	O00327-2
	BMAL1	ENST00000389707.8	TSL:1	c.-262-10191T>C		intron	N/A	ENSP00000374357.4	O00327-8
	BMAL1	ENST00000401424.6	TSL:1	c.-407-10191T>C		intron	N/A	ENSP00000385915.2	O00327-9

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20835 AN: 152034 Hom.: 1678 Cov.: 32

Gnomad AFR AF: 0.0485

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.137 AC: 20822 AN: 152152 Hom.: 1678 Cov.: 32 AF XY: 0.138 AC XY: 10253 AN XY: 74358

African (AFR) AF: 0.0484 AC: 2008 AN: 41528

American (AMR) AF: 0.172 AC: 2633 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3472

East Asian (EAS) AF: 0.293 AC: 1512 AN: 5154

South Asian (SAS) AF: 0.233 AC: 1117 AN: 4804

European-Finnish (FIN) AF: 0.130 AC: 1379 AN: 10604

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.160 AC: 10899 AN: 67982

Other (OTH) AF: 0.144 AC: 304 AN: 2116

Alfa AF: 0.150 Hom.: 4530

Bravo AF: 0.133

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.70
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10832020; hg19: chr11-13321343;