Variant 4-55952272-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_025009.5(CEP135):c.113+29T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000407 in 1,284,074 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

CEP135
NM_025009.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.98

Variant links:

Genes affected

CEP135 (HGNC:29086): (centrosomal protein 135) This gene encodes a centrosomal protein, which acts as a scaffolding protein during early centriole biogenesis, and is also required for centriole-centriole cohesion during interphase. Mutations in this gene are associated with autosomal recessive primary microcephaly-8. [provided by RefSeq, Jun 2012]

CEP135 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 4-55952272-T-G is Benign according to our data. Variant chr4-55952272-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1254843.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00206 (314/152340) while in subpopulation AFR AF= 0.00731 (304/41586). AF 95% confidence interval is 0.00663. There are 1 homozygotes in gnomad4. There are 166 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP135	NM_025009.5 linkuse as main transcript	c.113+29T>G		intron_variant		ENST00000257287.5	NP_079285.2
CEP135	XM_006714055.4 linkuse as main transcript	c.113+29T>G		intron_variant			XP_006714118.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP135	ENST00000257287.5 linkuse as main transcript	c.113+29T>G	intron_variant		1	NM_025009.5	ENSP00000257287	P1	Q66GS9-1
CEP135	ENST00000422247.6 linkuse as main transcript	c.113+29T>G	intron_variant		2		ENSP00000412799		Q66GS9-2
CEP135	ENST00000506809.1 linkuse as main transcript	n.302T>G	non_coding_transcript_exon_variant	2/2	3
CEP135	ENST00000706800.1 linkuse as main transcript	n.286+29T>G	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

314

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00733

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000414

AC:

101

AN:

243680

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

132140

show subpopulations

Gnomad AFR exome

AF:

0.00602

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000671

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000185

AC:

209

AN:

1131734

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

578804

show subpopulations

Gnomad4 AFR exome

AF:

0.00688

Gnomad4 AMR exome

AF:

0.000115

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000378

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000123

Gnomad4 OTH exome

AF:

0.000304

GnomAD4 genome

AF:

0.00206

AC:

314

AN:

152340

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

166

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00731

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000684

Hom.:

Bravo

AF:

0.00204

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 27, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0020

DANN

Benign

0.33

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over