rs2306074

chr12-27402853-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020183.6(BMAL2):c.1477+176T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,028 control chromosomes in the GnomAD database, including 11,225 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 0.37 (11225 hom., cov: 32)
• Consequence: BMAL2 NM_020183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

Genes affected

BMAL2 (HGNC:18984): (basic helix-loop-helix ARNT like 2) This gene encodes a basic helix-loop-helix transcription factor belonging to the PAS (PER, ARNT, SIM) superfamily. The PAS proteins play important roles in adaptation to low atmospheric and cellular oxygen levels, exposure to certain environmental pollutants, and diurnal oscillations in light and temperature. This protein forms a transcriptionally active heterodimer with the circadian CLOCK protein, the structurally related MOP4, and hypoxia-inducible factors, such as HIF1alpha. Consistent with its role as a biologically relevant partner of circadian and hypoxia factors, this protein is coexpressed in regions of the brain such as the thalamus, hypothalamus, and amygdala. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

BMAL2-AS1 (HGNC:49892): (BMAL2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL2	NM_020183.6	c.1477+176T>C		intron_variant		ENST00000266503.10
BMAL2-AS1	NR_109975.1	n.139-8230A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMAL2	ENST00000266503.10	c.1477+176T>C		intron_variant		1	NM_020183.6	P2
BMAL2-AS1	ENST00000500498.2	n.130-8230A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56646 AN: 151908 Hom.: 11207 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.373 AC: 56715 AN: 152028 Hom.: 11225 Cov.: 32 AF XY: 0.377 AC XY: 28004 AN XY: 74318

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.335

Alfa AF: 0.329 Hom.: 4678

Bravo AF: 0.368

Asia WGS AF: 0.562 AC: 1952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.21
Dann	Benign	0.41

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: rs2306074; hg19: chr12-27555786;