11-13352217-C-T

Variant names:

• chr11-13352217-C-T
• rs11022775
• NM_001297719.2:c.-8-2084C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297719.2(BMAL1):​c.-8-2084C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 151,998 control chromosomes in the GnomAD database, including 2,506 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 0.15 (2506 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-8-2084C>T		intron_variant	Intron 4 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.-8-2084C>T		intron_variant	Intron 4 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22159 AN: 151880 Hom.: 2496 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.0937

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.0374

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.146 AC: 22223 AN: 151998 Hom.: 2506 Cov.: 32 AF XY: 0.144 AC XY: 10709 AN XY: 74320

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0807

Gnomad4 EAS AF: 0.0939

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.0374

Gnomad4 NFE AF: 0.0752

Gnomad4 OTH AF: 0.138

Alfa AF: 0.0884 Hom.: 1147

Bravo AF: 0.158

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs11022775; hg19: chr11-13373764;