NM_015147.3:c.-46-3771G>T

Variant names:

• chr2-65065628-G-T
• rs2080385
• NM_015147.3:c.-46-3771G>T

Variant summary

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

The NM_015147.3(CEP68):​c.-46-3771G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,058 control chromosomes in the GnomAD database, including 6,869 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 0.29 (6869 hom., cov: 32)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

Genes affected

CEP68 (HGNC:29076): (centrosomal protein 68) Enables protein domain specific binding activity and protein kinase binding activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP68	NM_015147.3	c.-46-3771G>T		intron_variant	Intron 1 of 6	ENST00000377990.7	NP_055962.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.-46-3771G>T		intron_variant	Intron 1 of 6	1	NM_015147.3	ENSP00000367229.2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44476 AN: 151940 Hom.: 6838 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.293 AC: 44558 AN: 152058 Hom.: 6869 Cov.: 32 AF XY: 0.292 AC XY: 21669 AN XY: 74312

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.324

Alfa AF: 0.284 Hom.: 781

Bravo AF: 0.302

Asia WGS AF: 0.393 AC: 1365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.41
DANN	Benign	0.24

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: rs2080385; hg19: chr2-65292762;