3-138570379-C-T

Variant names:

• chr3-138570379-C-T
• rs1673607
• NM_024491.4:c.404G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024491.4(CEP70):​c.404G>A​(p.Ser135Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 1,603,188 control chromosomes in the GnomAD database, including 274,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.59 (27119 hom., cov: 31)
  • Exomes 𝑓: 0.58 (247223 hom.)
• Consequence: CEP70 NM_024491.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 40 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.2550677E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP70	NM_024491.4	c.404G>A	p.Ser135Asn	missense_variant	Exon 6 of 18	ENST00000264982.8	NP_077817.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP70	ENST00000264982.8	c.404G>A	p.Ser135Asn	missense_variant	Exon 6 of 18	1	NM_024491.4	ENSP00000264982.3

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89771 AN: 151796 Hom.: 27085 Cov.: 31

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.576

GnomAD2 exomes AF: 0.628 AC: 153590 AN: 244510 AF XY: 0.621

Gnomad AFR exome AF: 0.594

Gnomad AMR exome AF: 0.774

Gnomad ASJ exome AF: 0.499

Gnomad EAS exome AF: 0.954

Gnomad FIN exome AF: 0.627

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.599

GnomAD4 exome AF: 0.577 AC: 837866 AN: 1451274 Hom.: 247223 Cov.: 34 AF XY: 0.578 AC XY: 417446 AN XY: 722008

African (AFR) AF: 0.591 AC: 19495 AN: 32990

American (AMR) AF: 0.760 AC: 32769 AN: 43122

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 12913 AN: 26002

East Asian (EAS) AF: 0.949 AC: 37275 AN: 39280

South Asian (SAS) AF: 0.664 AC: 56110 AN: 84484

European-Finnish (FIN) AF: 0.629 AC: 33560 AN: 53360

Middle Eastern (MID) AF: 0.549 AC: 3155 AN: 5750

European-Non Finnish (NFE) AF: 0.549 AC: 607082 AN: 1106282

Other (OTH) AF: 0.592 AC: 35507 AN: 60004

GnomAD4 genome AF: 0.591 AC: 89851 AN: 151914 Hom.: 27119 Cov.: 31 AF XY: 0.600 AC XY: 44589 AN XY: 74260

African (AFR) AF: 0.584 AC: 24153 AN: 41378

American (AMR) AF: 0.670 AC: 10238 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1735 AN: 3470

East Asian (EAS) AF: 0.944 AC: 4898 AN: 5186

South Asian (SAS) AF: 0.672 AC: 3245 AN: 4830

European-Finnish (FIN) AF: 0.630 AC: 6629 AN: 10526

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37145 AN: 67924

Other (OTH) AF: 0.574 AC: 1211 AN: 2110

Alfa AF: 0.566 Hom.: 83014

Bravo AF: 0.598

TwinsUK AF: 0.557 AC: 2064

ALSPAC AF: 0.568 AC: 2189

ESP6500AA AF: 0.597 AC: 2629

ESP6500EA AF: 0.551 AC: 4739

ExAC AF: 0.624 AC: 75765

Asia WGS AF: 0.776 AC: 2696 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.6
DANN	Benign	0.28
DEOGEN2	Benign	0.022	T;T;.;.;T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.31	.;T;T;T;T;T;T
MetaRNN	Benign	7.3e-7	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.78	N;N;.;N;.;.;N
PhyloP100		0.19
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.35	N;N;N;N;N;N;N
REVEL	Benign	0.052
Sift	Benign	0.65	T;T;T;T;T;T;T
Sift4G	Benign	0.68	T;T;T;T;.;.;T
Polyphen		0.0	B;B;.;B;.;.;.
Vest4		0.021
MPC		0.041
ClinPred		0.00093	T
GERP RS		-0.47
Varity_R		0.026
gMVP		0.037
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1673607; hg19: chr3-138289221; COSMIC: COSV107299871; COSMIC: COSV107299871;