11-13307592-T-C

Variant names:

• chr11-13307592-T-C
• rs4757143
• NM_001297719.2:c.-262-2395T>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.-262-2395T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,214 control chromosomes in the GnomAD database, including 1,600 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 0.14 (1600 hom., cov: 32)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 10 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL1	NM_001297719.2	MANE Select	c.-262-2395T>C		intron	N/A	NP_001284648.1	O00327-2
	BMAL1	NM_001351807.2		c.-207-2395T>C		intron	N/A	NP_001338736.1
	BMAL1	NM_001351814.2		c.-262-2395T>C		intron	N/A	NP_001338743.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMAL1	ENST00000403290.6	TSL:1 MANE Select	c.-262-2395T>C		intron	N/A	ENSP00000384517.1	O00327-2
	BMAL1	ENST00000389707.8	TSL:1	c.-262-2395T>C		intron	N/A	ENSP00000374357.4	O00327-8
	BMAL1	ENST00000401424.6	TSL:1	c.-407-2395T>C		intron	N/A	ENSP00000385915.2	O00327-9

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21402 AN: 152096 Hom.: 1600 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.141 AC: 21417 AN: 152214 Hom.: 1600 Cov.: 32 AF XY: 0.145 AC XY: 10797 AN XY: 74418

African (AFR) AF: 0.121 AC: 5015 AN: 41528

American (AMR) AF: 0.148 AC: 2263 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3472

East Asian (EAS) AF: 0.171 AC: 884 AN: 5172

South Asian (SAS) AF: 0.222 AC: 1074 AN: 4832

European-Finnish (FIN) AF: 0.173 AC: 1831 AN: 10598

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9275 AN: 67994

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

Alfa AF: 0.139 Hom.: 2613

Bravo AF: 0.138

Asia WGS AF: 0.190 AC: 663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.79
PhyloP100		-0.18
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: rs4757143; hg19: chr11-13329139;