4-55955640-C-T

Variant names:

• chr4-55955640-C-T
• rs4865047
• NM_025009.5:c.472+1257C>T

Variant summary

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

The NM_025009.5(CEP135):​c.472+1257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,096 control chromosomes in the GnomAD database, including 1,536 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 0.13 (1536 hom., cov: 32)
• Consequence: CEP135 NM_025009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP135	NM_025009.5	c.472+1257C>T		intron_variant	Intron 4 of 25	ENST00000257287.5	NP_079285.2
CEP135	XM_006714055.4	c.472+1257C>T		intron_variant	Intron 4 of 25		XP_006714118.1
LOC124900705	XR_007058124.1	n.198-3169G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP135	ENST00000257287.5	c.472+1257C>T		intron_variant	Intron 4 of 25	1	NM_025009.5	ENSP00000257287.3
CEP135	ENST00000422247.6	c.472+1257C>T		intron_variant	Intron 4 of 5	2		ENSP00000412799.2
CEP135	ENST00000515081.1	n.106+1257C>T		intron_variant	Intron 1 of 4	2
CEP135	ENST00000706800.1	n.645+1257C>T		intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19275 AN: 151978 Hom.: 1530 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0636

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0855

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.127 AC: 19298 AN: 152096 Hom.: 1536 Cov.: 32 AF XY: 0.131 AC XY: 9720 AN XY: 74344

African (AFR) AF: 0.140 AC: 5796 AN: 41474

American (AMR) AF: 0.246 AC: 3756 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 657 AN: 3468

East Asian (EAS) AF: 0.257 AC: 1328 AN: 5170

South Asian (SAS) AF: 0.184 AC: 886 AN: 4812

European-Finnish (FIN) AF: 0.0636 AC: 673 AN: 10584

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0855 AC: 5815 AN: 68002

Other (OTH) AF: 0.135 AC: 285 AN: 2112

Alfa AF: 0.108 Hom.: 3447

Bravo AF: 0.140

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.40
PhyloP100		-0.25
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: rs4865047; hg19: chr4-56821806; COSMIC: COSV107229361; COSMIC: COSV107229361;