rs947599

Variant names:

• chr10-93506926-A-G
• rs947599
• NM_018131.5:c.460-62A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

CEP55 Gene-Disease associations (from GenCC):

• multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018131.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP55	NM_018131.5	MANE Select	c.460-62A>G		intron	N/A	NP_060601.4
	CEP55	NM_001127182.2		c.460-62A>G		intron	N/A	NP_001120654.2	Q53EZ4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP55	ENST00000371485.8	TSL:1 MANE Select	c.460-62A>G		intron	N/A	ENSP00000360540.3	Q53EZ4-1
	CEP55	ENST00000897343.1		c.460-62A>G		intron	N/A	ENSP00000567402.1
	CEP55	ENST00000912346.1		c.460-62A>G		intron	N/A	ENSP00000582405.1

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

African (AFR) AF: 0.304 AC: 6798 AN: 22344

American (AMR) AF: 0.474 AC: 20798 AN: 43878

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 12672 AN: 22498

East Asian (EAS) AF: 0.119 AC: 4412 AN: 37086

South Asian (SAS) AF: 0.590 AC: 44033 AN: 74642

European-Finnish (FIN) AF: 0.562 AC: 29815 AN: 53042

Middle Eastern (MID) AF: 0.551 AC: 2583 AN: 4688

European-Non Finnish (NFE) AF: 0.576 AC: 338636 AN: 588406

Other (OTH) AF: 0.528 AC: 21929 AN: 41494

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

African (AFR) AF: 0.311 AC: 12899 AN: 41480

American (AMR) AF: 0.519 AC: 7935 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1941 AN: 3472

East Asian (EAS) AF: 0.148 AC: 766 AN: 5176

South Asian (SAS) AF: 0.581 AC: 2798 AN: 4816

European-Finnish (FIN) AF: 0.556 AC: 5875 AN: 10568

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38979 AN: 67958

Other (OTH) AF: 0.510 AC: 1077 AN: 2110

Alfa AF: 0.538 Hom.: 76277

Bravo AF: 0.464

Asia WGS AF: 0.377 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.45
PhyloP100		0.071
PromoterAI		0.0050	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs947599; hg19: chr10-95266683; COSMIC: COSV65186244; COSMIC: COSV65186244;