11-13346203-T-C

Variant names:

• chr11-13346203-T-C
• rs3816360
• NM_001297719.2:c.-134-3742T>C

Variant summary

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

The NM_001297719.2(BMAL1):​c.-134-3742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,136 control chromosomes in the GnomAD database, including 26,310 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 0.58 (26310 hom., cov: 33)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• Publications: 27 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-134-3742T>C		intron_variant	Intron 3 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.-134-3742T>C		intron_variant	Intron 3 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88201 AN: 152018 Hom.: 26307 Cov.: 33

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.580 AC: 88236 AN: 152136 Hom.: 26310 Cov.: 33 AF XY: 0.569 AC XY: 42319 AN XY: 74366

African (AFR) AF: 0.527 AC: 21852 AN: 41480

American (AMR) AF: 0.505 AC: 7725 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2090 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1707 AN: 5166

South Asian (SAS) AF: 0.524 AC: 2529 AN: 4828

European-Finnish (FIN) AF: 0.519 AC: 5499 AN: 10592

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44958 AN: 68008

Other (OTH) AF: 0.610 AC: 1284 AN: 2104

Alfa AF: 0.630 Hom.: 27277

Bravo AF: 0.578

Asia WGS AF: 0.434 AC: 1512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.67
PhyloP100		-0.20
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: rs3816360; hg19: chr11-13367750;