11-13291422-G-T

Position:

• chr11-13291422-G-T

Variant summary

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

The NM_001297719.2(BMAL1):​c.-263+13499G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 151,998 control chromosomes in the GnomAD database, including 5,719 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 0.27 (5719 hom., cov: 31)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL1	NM_001297719.2	c.-263+13499G>T		intron_variant		ENST00000403290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL1	ENST00000403290.6	c.-263+13499G>T		intron_variant		1	NM_001297719.2	P4

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41284 AN: 151880 Hom.: 5719 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.272 AC: 41289 AN: 151998 Hom.: 5719 Cov.: 31 AF XY: 0.273 AC XY: 20269 AN XY: 74308

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.249

Alfa AF: 0.258 Hom.: 7958

Bravo AF: 0.271

Asia WGS AF: 0.356 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.43

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: rs7107287; hg19: chr11-13312969;