rs6486121

Variant names:

• chr11-13334223-C-T
• rs6486121
• NM_001297719.2:c.-135+7756C>T

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+7756C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,948 control chromosomes in the GnomAD database, including 21,984 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 0.52 (21984 hom., cov: 31)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 54 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.62 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+7756C>T		intron	N/A	NP_001284648.1	O00327-2
	BMAL1	NM_001351807.2		c.-134-15722C>T		intron	N/A	NP_001338736.1
	BMAL1	NM_001351814.2		c.-135+7756C>T		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+7756C>T		intron	N/A	ENSP00000384517.1	O00327-2
	BMAL1	ENST00000389707.8	TSL:1	c.-135+7756C>T		intron	N/A	ENSP00000374357.4	O00327-8
	BMAL1	ENST00000401424.6	TSL:1	c.-334-15722C>T		intron	N/A	ENSP00000385915.2	O00327-9

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79405 AN: 151830 Hom.: 21981 Cov.: 31

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.523 AC: 79436 AN: 151948 Hom.: 21984 Cov.: 31 AF XY: 0.514 AC XY: 38136 AN XY: 74252

African (AFR) AF: 0.416 AC: 17214 AN: 41414

American (AMR) AF: 0.531 AC: 8112 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2042 AN: 3468

East Asian (EAS) AF: 0.142 AC: 731 AN: 5160

South Asian (SAS) AF: 0.419 AC: 2016 AN: 4812

European-Finnish (FIN) AF: 0.482 AC: 5090 AN: 10554

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.625 AC: 42465 AN: 67956

Other (OTH) AF: 0.571 AC: 1201 AN: 2104

Alfa AF: 0.597 Hom.: 79969

Bravo AF: 0.525

Asia WGS AF: 0.316 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.061
DANN	Benign	0.48
PhyloP100		-1.9
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: rs6486121; hg19: chr11-13355770;