rs3897902

Variant names:

• chr11-13380256-C-A
• rs3897902
• NM_001297719.2:c.1524-905C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-13380256-C-A
• chr11-13380256-C-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.1524-905C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,136 control chromosomes in the GnomAD database, including 46,238 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 0.77 (46236 hom., cov: 32)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: BMAL1 NM_001297719.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 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.1524-905C>A		intron	N/A	NP_001284648.1	O00327-2
	BMAL1	NM_001351807.2		c.1539-905C>A		intron	N/A	NP_001338736.1
	BMAL1	NM_001351814.2		c.1539-905C>A		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.1524-905C>A		intron	N/A	ENSP00000384517.1	O00327-2
	BMAL1	ENST00000389707.8	TSL:1	c.1521-905C>A		intron	N/A	ENSP00000374357.4	O00327-8
	BMAL1	ENST00000403482.7	TSL:1	c.1518-905C>A		intron	N/A	ENSP00000385897.3	O00327-7

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117520 AN: 152016 Hom.: 46203 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.781

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 4 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.773 AC: 117609 AN: 152132 Hom.: 46236 Cov.: 32 AF XY: 0.774 AC XY: 57591 AN XY: 74366

African (AFR) AF: 0.665 AC: 27576 AN: 41470

American (AMR) AF: 0.776 AC: 11859 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2878 AN: 3472

East Asian (EAS) AF: 0.473 AC: 2445 AN: 5166

South Asian (SAS) AF: 0.817 AC: 3932 AN: 4814

European-Finnish (FIN) AF: 0.876 AC: 9291 AN: 10602

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 57036 AN: 68008

Other (OTH) AF: 0.776 AC: 1639 AN: 2112

Alfa AF: 0.779 Hom.: 4061

Bravo AF: 0.756

Asia WGS AF: 0.644 AC: 2241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.058
DANN	Benign	0.79
PhyloP100		-2.9
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: rs3897902; hg19: chr11-13401803;