11-13358241-T-C

Variant names:

• chr11-13358241-T-C
• rs2290036
• NM_001297719.2:c.222-193T>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.222-193T>C 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 152,210 control chromosomes in the GnomAD database, including 2,407 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 (2407 hom., cov: 33)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824
• Publications: 9 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]

LOC124902636 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297719.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL1	NM_001297719.2	MANE Select	c.222-193T>C		intron	N/A	NP_001284648.1
	BMAL1	NM_001351807.2		c.222-193T>C		intron	N/A	NP_001338736.1
	BMAL1	NM_001351814.2		c.222-193T>C		intron	N/A	NP_001338743.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL1	ENST00000403290.6	TSL:1 MANE Select	c.222-193T>C		intron	N/A	ENSP00000384517.1
	BMAL1	ENST00000389707.8	TSL:1	c.222-193T>C		intron	N/A	ENSP00000374357.4
	BMAL1	ENST00000403482.7	TSL:1	c.216-193T>C		intron	N/A	ENSP00000385897.3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23319 AN: 152092 Hom.: 2390 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0893

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0881

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.154 AC: 23384 AN: 152210 Hom.: 2407 Cov.: 33 AF XY: 0.155 AC XY: 11513 AN XY: 74432

African (AFR) AF: 0.290 AC: 12022 AN: 41498

American (AMR) AF: 0.111 AC: 1705 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3470

East Asian (EAS) AF: 0.156 AC: 809 AN: 5186

South Asian (SAS) AF: 0.207 AC: 1000 AN: 4830

European-Finnish (FIN) AF: 0.113 AC: 1193 AN: 10584

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0881 AC: 5992 AN: 68018

Other (OTH) AF: 0.140 AC: 297 AN: 2114

Alfa AF: 0.119 Hom.: 576

Bravo AF: 0.159

Asia WGS AF: 0.184 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		-0.82
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: rs2290036; hg19: chr11-13379788;