rs947599

Positions:

• chr10-93506926-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018131.5(CEP55):​c.460-62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,040,150 control chromosomes in the GnomAD database, including 154,555 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 0.48 (18965 hom., cov: 32)
  • Exomes 𝑓: 0.54 (135590 hom.)
• Consequence: CEP55 NM_018131.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

Genes affected

CEP55 (HGNC:1161): (centrosomal protein 55) Enables identical protein binding activity. Involved in cranial skeletal system development; establishment of protein localization; and midbody abscission. Acts upstream of or within mitotic cytokinesis. Located in Flemming body; centriolar satellite; and plasma membrane. Implicated in multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP55	NM_018131.5	c.460-62A>G		intron_variant		ENST00000371485.8	NP_060601.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP55	ENST00000371485.8	c.460-62A>G		intron_variant		1	NM_018131.5	ENSP00000360540	P1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73075 AN: 151954 Hom.: 18961 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.542 AC: 481676 AN: 888078 Hom.: 135590 AF XY: 0.547 AC XY: 254815 AN XY: 466058

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.474

Gnomad4 ASJ exome AF: 0.563

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.590

Gnomad4 FIN exome AF: 0.562

Gnomad4 NFE exome AF: 0.576

Gnomad4 OTH exome AF: 0.528

GnomAD4 genome AF: 0.481 AC: 73092 AN: 152072 Hom.: 18965 Cov.: 32 AF XY: 0.480 AC XY: 35718 AN XY: 74336

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.510

Alfa AF: 0.557 Hom.: 48625

Bravo AF: 0.464

Asia WGS AF: 0.377 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs947599; hg19: chr10-95266683; COSMIC: COSV65186244; COSMIC: COSV65186244;