Genetic Variant CEP131:p.Arg74Arg (chr17-81208978-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014984.4(CEP131):c.222A>G(p.Arg74Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,612,972 control chromosomes in the GnomAD database, including 179,919 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 0.38 ( 13875 hom., cov: 32)

Exomes 𝑓: 0.47 ( 166044 hom. )

Consequence

CEP131
NM_014984.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.815

Variant links:

Genes affected

CEP131 (HGNC:29511): (centrosomal protein 131) Enables protein homodimerization activity. Involved in several processes, including intraciliary transport involved in cilium assembly; protein localization to centrosome; and regulation of centrosome duplication. Located in several cellular components, including ciliary transition zone; intercellular bridge; and microtubule organizing center. Colocalizes with centrosome. [provided by Alliance of Genome Resources, Apr 2022]

CEP131 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP7

Synonymous conserved (PhyloP=-0.815 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP131	NM_014984.4 link	c.222A>G	p.Arg74Arg	synonymous_variant	Exon 3 of 26	ENST00000450824.7	NP_055799.2	Q9UPN4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEP131	ENST00000450824.7 link	c.222A>G	p.Arg74Arg	synonymous_variant	Exon 3 of 26	1	NM_014984.4	ENSP00000393583.2	Q9UPN4-2
CEP131	ENST00000269392.8 link	c.222A>G	p.Arg74Arg	synonymous_variant	Exon 3 of 26	1		ENSP00000269392.4	Q9UPN4-1
CEP131	ENST00000575907.5 link	c.222A>G	p.Arg74Arg	synonymous_variant	Exon 3 of 25	1		ENSP00000459733.1	I3L2J8
CEP131	ENST00000374782.7 link	c.222A>G	p.Arg74Arg	synonymous_variant	Exon 3 of 25	5		ENSP00000363914.3	Q9UPN4-3

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58196

AN:

151856

Hom.:

13865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0912

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.574

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.556

Gnomad FIN

AF:

0.525

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.460

Gnomad OTH

AF:

0.401

GnomAD3 exomes

AF:

0.503

AC:

125608

AN:

249564

Hom.:

34182

AF XY:

0.504

AC XY:

68210

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.0809

Gnomad AMR exome

AF:

0.691

Gnomad ASJ exome

AF:

0.571

Gnomad EAS exome

AF:

0.654

Gnomad SAS exome

AF:

0.549

Gnomad FIN exome

AF:

0.505

Gnomad NFE exome

AF:

0.465

Gnomad OTH exome

AF:

0.483

GnomAD4 exome

AF:

0.469

AC:

684529

AN:

1460998

Hom.:

166044

Cov.:

AF XY:

0.471

AC XY:

342411

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.0754

Gnomad4 AMR exome

AF:

0.676

Gnomad4 ASJ exome

AF:

0.568

Gnomad4 EAS exome

AF:

0.647

Gnomad4 SAS exome

AF:

0.551

Gnomad4 FIN exome

AF:

0.499

Gnomad4 NFE exome

AF:

0.456

Gnomad4 OTH exome

AF:

0.459

GnomAD4 genome

AF:

0.383

AC:

58210

AN:

151974

Hom.:

13875

Cov.:

AF XY:

0.393

AC XY:

29192

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.0909

Gnomad4 AMR

AF:

0.556

Gnomad4 ASJ

AF:

0.574

Gnomad4 EAS

AF:

0.634

Gnomad4 SAS

AF:

0.557

Gnomad4 FIN

AF:

0.525

Gnomad4 NFE

AF:

0.460

Gnomad4 OTH

AF:

0.404

Alfa

AF:

0.420

Hom.:

7622

Bravo

AF:

0.374

Asia WGS

AF:

0.574

AC:

1995

AN:

3478

EpiCase

AF:

0.468

EpiControl

AF:

0.469

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

DANN

Benign

0.46

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over