11-13375263-G-A

Variant names:

• chr11-13375263-G-A
• rs11022779
• NM_001297719.2:c.1175-349G>A

Variant summary

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

The NM_001297719.2(BMAL1):​c.1175-349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,178 control chromosomes in the GnomAD database, including 2,079 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 0.15 (2079 hom., cov: 33)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.1175-349G>A		intron_variant	Intron 14 of 19	ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.1175-349G>A		intron_variant	Intron 14 of 19	1	NM_001297719.2	ENSP00000384517.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23429 AN: 152060 Hom.: 2077 Cov.: 33

Gnomad AFR AF: 0.0706

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.154 AC: 23455 AN: 152178 Hom.: 2079 Cov.: 33 AF XY: 0.155 AC XY: 11519 AN XY: 74398

African (AFR) AF: 0.0709 AC: 2946 AN: 41542

American (AMR) AF: 0.217 AC: 3321 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3472

East Asian (EAS) AF: 0.149 AC: 770 AN: 5184

South Asian (SAS) AF: 0.101 AC: 487 AN: 4820

European-Finnish (FIN) AF: 0.235 AC: 2486 AN: 10564

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.185 AC: 12567 AN: 67992

Other (OTH) AF: 0.150 AC: 318 AN: 2116

Alfa AF: 0.169 Hom.: 366

Bravo AF: 0.151

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.5
DANN	Benign	0.46
PhyloP100		0.25
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: rs11022779; hg19: chr11-13396810;