11-13369313-T-G

Variant names:

• chr11-13369313-T-G
• rs11022778
• NM_001297719.2:c.671-305T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297719.2(BMAL1):​c.671-305T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,082 control chromosomes in the GnomAD database, including 6,760 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 0.29 (6760 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455
• Publications: 24 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.671-305T>G		intron_variant	Intron 11 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.671-305T>G		intron_variant	Intron 11 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44438 AN: 151964 Hom.: 6754 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.292 AC: 44465 AN: 152082 Hom.: 6760 Cov.: 32 AF XY: 0.295 AC XY: 21921 AN XY: 74326

African (AFR) AF: 0.215 AC: 8915 AN: 41482

American (AMR) AF: 0.338 AC: 5171 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1102 AN: 3470

East Asian (EAS) AF: 0.154 AC: 796 AN: 5178

South Asian (SAS) AF: 0.426 AC: 2052 AN: 4812

European-Finnish (FIN) AF: 0.286 AC: 3019 AN: 10570

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22278 AN: 67976

Other (OTH) AF: 0.328 AC: 691 AN: 2106

Alfa AF: 0.314 Hom.: 25106

Bravo AF: 0.292

Asia WGS AF: 0.298 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.91
DANN	Benign	0.54
PhyloP100		-0.46
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: rs11022778; hg19: chr11-13390860;