11-13362135-C-T

Variant names:

• chr11-13362135-C-T
• rs1868049
• NM_001297719.2:c.459+1711C>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.459+1711C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,118 control chromosomes in the GnomAD database, including 1,985 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 (1985 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.459+1711C>T		intron_variant	Intron 9 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.459+1711C>T		intron_variant	Intron 9 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20969 AN: 152000 Hom.: 1986 Cov.: 32

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.138 AC: 20957 AN: 152118 Hom.: 1985 Cov.: 32 AF XY: 0.140 AC XY: 10382 AN XY: 74354

African (AFR) AF: 0.0626 AC: 2599 AN: 41530

American (AMR) AF: 0.108 AC: 1655 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2718 AN: 5148

South Asian (SAS) AF: 0.191 AC: 918 AN: 4818

European-Finnish (FIN) AF: 0.157 AC: 1663 AN: 10584

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.152 AC: 10365 AN: 67976

Other (OTH) AF: 0.128 AC: 271 AN: 2116

Alfa AF: 0.142 Hom.: 2626

Bravo AF: 0.132

Asia WGS AF: 0.318 AC: 1105 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.041
DANN	Benign	0.53
PhyloP100		-1.2
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: rs1868049; hg19: chr11-13383682;