chr11-13339977-C-T

Variant names:

• chr11-13339977-C-T
• rs6486122
• NM_001297719.2:c.-134-9968C>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.-134-9968C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,056 control chromosomes in the GnomAD database, including 36,756 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 0.69 (36756 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• Publications: 35 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.82 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.-134-9968C>T		intron	N/A	NP_001284648.1	O00327-2
	BMAL1	NM_001351807.2		c.-134-9968C>T		intron	N/A	NP_001338736.1
	BMAL1	NM_001351814.2		c.-134-9968C>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.-134-9968C>T		intron	N/A	ENSP00000384517.1	O00327-2
	BMAL1	ENST00000389707.8	TSL:1	c.-134-9968C>T		intron	N/A	ENSP00000374357.4	O00327-8
	BMAL1	ENST00000401424.6	TSL:1	c.-334-9968C>T		intron	N/A	ENSP00000385915.2	O00327-9

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104054 AN: 151938 Hom.: 36693 Cov.: 32

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.685 AC: 104183 AN: 152056 Hom.: 36756 Cov.: 32 AF XY: 0.673 AC XY: 50015 AN XY: 74304

African (AFR) AF: 0.827 AC: 34327 AN: 41490

American (AMR) AF: 0.626 AC: 9562 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2127 AN: 3464

East Asian (EAS) AF: 0.334 AC: 1722 AN: 5152

South Asian (SAS) AF: 0.550 AC: 2650 AN: 4814

European-Finnish (FIN) AF: 0.529 AC: 5587 AN: 10554

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46137 AN: 67982

Other (OTH) AF: 0.695 AC: 1466 AN: 2110

Alfa AF: 0.676 Hom.: 55491

Bravo AF: 0.701

Asia WGS AF: 0.474 AC: 1651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.3
DANN	Benign	0.66
PhyloP100		-0.33
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: rs6486122; hg19: chr11-13361524;