11-13276938-T-C

Position:

• chr11-13276938-T-C

Variant summary

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

The ENST00000702886.1(ENSG00000290083):​n.466A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,194 control chromosomes in the GnomAD database, including 30,125 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 0.62 (30122 hom., cov: 35)
  • Exomes 𝑓: 0.80 (3 hom.)
• Consequence: ENST00000702886.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811

Genes affected

(HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMAL1	NM_001351804.1	c.-397T>C		5_prime_UTR_variant	1/20
BMAL1	XM_011520105.4	c.-87T>C		5_prime_UTR_variant	1/18
BMAL1	XM_011520107.4	c.-87T>C		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000702886.1	n.466A>G		non_coding_transcript_exon_variant	1/1
BMAL1	ENST00000529050.5	c.-216T>C		5_prime_UTR_variant	1/3	4
BMAL1	ENST00000534544.5	c.-342T>C		5_prime_UTR_variant	1/5	5

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94238 AN: 152066 Hom.: 30089 Cov.: 35

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.800 AC: 8 AN: 10 Hom.: 3 Cov.: 0 AF XY: 0.667 AC XY: 4 AN XY: 6

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.620 AC: 94324 AN: 152184 Hom.: 30122 Cov.: 35 AF XY: 0.622 AC XY: 46298 AN XY: 74392

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.640

Alfa AF: 0.669 Hom.: 8689

Bravo AF: 0.607

Asia WGS AF: 0.604 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2279287; hg19: chr11-13298485;