rs3897902

Positions:

• chr11-13380256-C-A
• chr11-13380256-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

BMAL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMAL1	NM_001297719.2	c.1524-905C>A		intron_variant		ENST00000403290.6	NP_001284648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMAL1	ENST00000403290.6	c.1524-905C>A		intron_variant		1	NM_001297719.2	ENSP00000384517.1

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

Gnomad4 NFE exome AF: 1.00

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

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.876

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.776

Alfa AF: 0.784 Hom.: 3864

Bravo AF: 0.756

Asia WGS AF: 0.644 AC: 2241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.058
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs3897902; hg19: chr11-13401803;