Genetic Variant CEP131:c.272+61T>C (chr17-81208867-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014984.4(CEP131):c.272+61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 1,326,124 control chromosomes in the GnomAD database, including 597,395 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 0.92 ( 65215 hom., cov: 31)

Exomes 𝑓: 0.95 ( 532180 hom. )

Consequence

CEP131
NM_014984.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.38

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

CEP131 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP131	NM_014984.4 link	c.272+61T>C		intron_variant	Intron 3 of 25	ENST00000450824.7	NP_055799.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CEP131	ENST00000450824.7 link	c.272+61T>C	intron_variant	Intron 3 of 25	1	NM_014984.4	ENSP00000393583.2
CEP131	ENST00000269392.8 link	c.272+61T>C	intron_variant	Intron 3 of 25	1		ENSP00000269392.4
CEP131	ENST00000575907.5 link	c.272+61T>C	intron_variant	Intron 3 of 24	1		ENSP00000459733.1
CEP131	ENST00000374782.7 link	c.272+61T>C	intron_variant	Intron 3 of 24	5		ENSP00000363914.3

Frequencies

GnomAD3 genomes

AF:

0.924

AC:

140561

AN:

152044

Hom.:

65170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.848

Gnomad AMI

AF:

0.941

Gnomad AMR

AF:

0.947

Gnomad ASJ

AF:

0.966

Gnomad EAS

AF:

0.870

Gnomad SAS

AF:

0.897

Gnomad FIN

AF:

0.972

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.962

Gnomad OTH

AF:

0.928

GnomAD4 exome

AF:

0.952

AC:

1117166

AN:

1173962

Hom.:

532180

AF XY:

0.950

AC XY:

566126

AN XY:

595942

show subpopulations

African (AFR)

AF:

0.847

AC:

23739

AN:

28042

American (AMR)

AF:

0.953

AC:

38583

AN:

40486

Ashkenazi Jewish (ASJ)

AF:

0.969

AC:

22775

AN:

23498

East Asian (EAS)

AF:

0.872

AC:

32951

AN:

37808

South Asian (SAS)

AF:

0.895

AC:

70289

AN:

78506

European-Finnish (FIN)

AF:

0.967

AC:

48131

AN:

49774

Middle Eastern (MID)

AF:

0.951

AC:

3554

AN:

3738

European-Non Finnish (NFE)

AF:

0.963

AC:

829310

AN:

861296

Other (OTH)

AF:

0.941

AC:

47834

AN:

50814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

2573

5146

7719

10292

12865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15044

30088

45132

60176

75220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.924

AC:

140662

AN:

152162

Hom.:

65215

Cov.:

AF XY:

0.924

AC XY:

68760

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.849

AC:

35242

AN:

41532

American (AMR)

AF:

0.947

AC:

14487

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.966

AC:

3353

AN:

3472

East Asian (EAS)

AF:

0.869

AC:

4457

AN:

5126

South Asian (SAS)

AF:

0.897

AC:

4322

AN:

4820

European-Finnish (FIN)

AF:

0.972

AC:

10317

AN:

10614

Middle Eastern (MID)

AF:

0.929

AC:

273

AN:

294

European-Non Finnish (NFE)

AF:

0.962

AC:

65396

AN:

67986

Other (OTH)

AF:

0.929

AC:

1961

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

531

1061

1592

2122

2653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.939

Hom.:

8693

Bravo

AF:

0.919

Asia WGS

AF:

0.872

AC:

3033

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.21

(source)

DANN

Benign

0.42

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over