rs1562438

Positions:

• chr11-13342653-C-T

Variant summary

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

The NM_001297719.2(BMAL1):​c.-134-7292C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,008 control chromosomes in the GnomAD database, including 6,291 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 0.26 (6291 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL1	NM_001297719.2	c.-134-7292C>T		intron_variant		ENST00000403290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL1	ENST00000403290.6	c.-134-7292C>T		intron_variant		1	NM_001297719.2	P4

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39663 AN: 151888 Hom.: 6288 Cov.: 32

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.261 AC: 39671 AN: 152008 Hom.: 6291 Cov.: 32 AF XY: 0.269 AC XY: 19966 AN XY: 74302

Gnomad4 AFR AF: 0.0905

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.250

Alfa AF: 0.285 Hom.: 5439

Bravo AF: 0.258

Asia WGS AF: 0.374 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.63

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: rs1562438; hg19: chr11-13364200;