14-77116140-G-T

Position:

• chr14-77116140-G-T

Variant summary

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

The NM_033426.3(CIPC):​c.*1822G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 152,340 control chromosomes in the GnomAD database, including 71,784 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 0.97 (71783 hom., cov: 34)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: CIPC NM_033426.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466

Genes affected

CIPC (HGNC:20365): (CLOCK interacting pacemaker) Predicted to be involved in negative regulation of circadian rhythm and negative regulation of transcription, DNA-templated. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259164 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIPC	NM_033426.3	c.*1822G>T		3_prime_UTR_variant	4/4	ENST00000361786.7	NP_219494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIPC	ENST00000361786.7	c.*1822G>T		3_prime_UTR_variant	4/4	1	NM_033426.3	ENSP00000355319.2
ENSG00000259164	ENST00000557752.1	n.136+10296G>T		intron_variant		5		ENSP00000456507.1

Frequencies

GnomAD3 genomes AF: 0.970 AC: 147653 AN: 152220 Hom.: 71732 Cov.: 34

Gnomad AFR AF: 0.903

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.972

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.970 AC: 147762 AN: 152338 Hom.: 71783 Cov.: 34 AF XY: 0.972 AC XY: 72436 AN XY: 74494

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.988

Gnomad4 ASJ AF: 0.976

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.994

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.973

Alfa AF: 0.991 Hom.: 81778

Bravo AF: 0.966

Asia WGS AF: 0.995 AC: 3461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.0
DANN	Benign	0.56

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: rs10483881; hg19: chr14-77582483;