11-13285101-A-G

Variant names:

• chr11-13285101-A-G
• rs4146387
• NM_001297719.2:c.-263+7178A>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.-263+7178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 152,296 control chromosomes in the GnomAD database, including 70,593 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 0.96 (70593 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.-263+7178A>G		intron_variant	Intron 1 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.-263+7178A>G		intron_variant	Intron 1 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146489 AN: 152176 Hom.: 70539 Cov.: 32

Gnomad AFR AF: 0.934

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.967

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.945

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

GnomAD4 genome AF: 0.963 AC: 146603 AN: 152296 Hom.: 70593 Cov.: 32 AF XY: 0.963 AC XY: 71739 AN XY: 74472

African (AFR) AF: 0.934 AC: 38777 AN: 41534

American (AMR) AF: 0.967 AC: 14802 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3185 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5180 AN: 5182

South Asian (SAS) AF: 0.947 AC: 4574 AN: 4830

European-Finnish (FIN) AF: 0.987 AC: 10485 AN: 10618

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.976 AC: 66428 AN: 68034

Other (OTH) AF: 0.946 AC: 2001 AN: 2116

Alfa AF: 0.966 Hom.: 23379

Bravo AF: 0.960

Asia WGS AF: 0.974 AC: 3387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	7.7
DANN	Benign	0.66
PhyloP100		0.23
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: rs4146387; hg19: chr11-13306648;