rs2593068

Variant names:

• chr4-55963316-G-A
• rs2593068
• NM_025009.5:c.700-958G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-55963316-G-A
• chr4-55963316-G-C

Variant summary

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

The NM_025009.5(CEP135):​c.700-958G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,998 control chromosomes in the GnomAD database, including 23,864 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 0.55 (23864 hom., cov: 33)
• Consequence: CEP135 NM_025009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• microcephaly 8, primary, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124900705 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP135	NM_025009.5	c.700-958G>A		intron_variant	Intron 6 of 25	ENST00000257287.5	NP_079285.2
CEP135	XM_006714055.4	c.700-958G>A		intron_variant	Intron 6 of 25		XP_006714118.1
LOC124900705	XR_007058124.1	n.197+7457C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP135	ENST00000257287.5	c.700-958G>A		intron_variant	Intron 6 of 25	1	NM_025009.5	ENSP00000257287.3
CEP135	ENST00000515081.1	n.334-958G>A		intron_variant	Intron 3 of 4	2

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84140 AN: 151880 Hom.: 23810 Cov.: 33

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.577

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.554 AC: 84243 AN: 151998 Hom.: 23864 Cov.: 33 AF XY: 0.557 AC XY: 41357 AN XY: 74252

African (AFR) AF: 0.668 AC: 27680 AN: 41462

American (AMR) AF: 0.612 AC: 9339 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1972 AN: 3472

East Asian (EAS) AF: 0.422 AC: 2180 AN: 5170

South Asian (SAS) AF: 0.464 AC: 2236 AN: 4822

European-Finnish (FIN) AF: 0.552 AC: 5821 AN: 10538

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33100 AN: 67962

Other (OTH) AF: 0.581 AC: 1227 AN: 2112

Alfa AF: 0.511 Hom.: 77759

Bravo AF: 0.567

Asia WGS AF: 0.521 AC: 1810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.67
DANN	Benign	0.59
PhyloP100		0.080
Mutation Taster		=100/0	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: rs2593068; hg19: chr4-56829482;