3-138497928-C-G

Position:

• chr3-138497928-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024491.4(CEP70):​c.1732+103G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000374 in 1,532,212 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (5 hom.)
• Consequence: CEP70 NM_024491.4 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.105

Genes affected

CEP70 (HGNC:29972): (centrosomal protein 70) Enables identical protein binding activity. Predicted to be involved in cilium assembly and regulation of microtubule cytoskeleton organization. Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP70	NM_024491.4	c.1732+103G>C		intron_variant		ENST00000264982.8	NP_077817.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP70	ENST00000264982.8	c.1732+103G>C		intron_variant		1	NM_024491.4	ENSP00000264982.3

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000388 AC: 536 AN: 1379902 Hom.: 5 Cov.: 31 AF XY: 0.000389 AC XY: 266 AN XY: 683140

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000650

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0123

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.000368

Gnomad4 NFE exome AF: 0.0000464

Gnomad4 OTH exome AF: 0.000245

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74490

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.000170

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Median cleft lip and palate Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Reproductive Medicine, Peking University Third Hospital

Oct 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.0
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: rs200041935; hg19: chr3-138216770;