4-55952526-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_025009.5(CEP135):c.113+283C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 248,166 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (12 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (2 hom.)
• Consequence: CEP135 NM_025009.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.750

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]

LOC124900705 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-55952526-C-T is Benign according to our data. Variant chr4-55952526-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1198071.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00554 (844/152264) while in subpopulation NFE AF= 0.00384 (261/68020). AF 95% confidence interval is 0.00345. There are 12 homozygotes in gnomad4. There are 552 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP135	NM_025009.5	c.113+283C>T		intron_variant		ENST00000257287.5
LOC124900705	XR_007058124.1	n.198-55G>A		intron_variant, non_coding_transcript_variant
CEP135	XM_006714055.4	c.113+283C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP135	ENST00000257287.5	c.113+283C>T		intron_variant		1	NM_025009.5	P1
CEP135	ENST00000422247.6	c.113+283C>T		intron_variant		2
CEP135	ENST00000506809.1	n.556C>T		non_coding_transcript_exon_variant	2/2	3
CEP135	ENST00000706800.1	n.286+283C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00555 AC: 844 AN: 152146 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0485

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00384

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00298 AC: 286 AN: 95902 Hom.: 2 Cov.: 0 AF XY: 0.00316 AC XY: 155 AN XY: 49102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000249

Gnomad4 ASJ exome AF: 0.000249

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0272

Gnomad4 NFE exome AF: 0.00256

Gnomad4 OTH exome AF: 0.00204

GnomAD4 genome AF: 0.00554 AC: 844 AN: 152264 Hom.: 12 Cov.: 33 AF XY: 0.00741 AC XY: 552 AN XY: 74458

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0485

Gnomad4 NFE AF: 0.00384

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00556 Hom.: 1

Bravo AF: 0.00200

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.1
Dann	Benign	0.30

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: rs192716308; hg19: chr4-56818692;