14-80526987-A-G

Variant summary

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

The NM_152446.5(CEP128):c.2959-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (3 hom., cov: 0)
  • Exomes 𝑓: 0.00039 (1 hom.)
• Consequence: CEP128 NM_152446.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00009166
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0710

Genes affected

CEP128 (HGNC:20359): (centrosomal protein 128) Involved in protein localization. Located in centriole and spindle pole. Part of centriolar subdistal appendage. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 14-80526987-A-G is Benign according to our data. Variant chr14-80526987-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 722985.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0391 (468/11978) while in subpopulation AMR AF= 0.0633 (19/300). AF 95% confidence interval is 0.0415. There are 3 homozygotes in gnomad4. There are 224 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP128	NM_152446.5	c.2959-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000555265.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP128	ENST00000555265.6	c.2959-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_152446.5	P2

Frequencies

GnomAD3 genomes AF: 0.0391 AC: 468 AN: 11964 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00410

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00425

Gnomad OTH AF: 0.0366

GnomAD3 exomes AF: 0.0260 AC: 299 AN: 11478 Hom.: 50 AF XY: 0.0250 AC XY: 150 AN XY: 5992

Gnomad AFR exome AF: 0.0521

Gnomad AMR exome AF: 0.0610

Gnomad ASJ exome AF: 0.0186

Gnomad EAS exome AF: 0.0137

Gnomad SAS exome AF: 0.00972

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0132

Gnomad OTH exome AF: 0.0185

GnomAD4 exome AF: 0.000392 AC: 408 AN: 1041654 Hom.: 1 Cov.: 19 AF XY: 0.000367 AC XY: 193 AN XY: 525358

Gnomad4 AFR exome AF: 0.0164

Gnomad4 AMR exome AF: 0.00142

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000264

Gnomad4 OTH exome AF: 0.000876

GnomAD4 genome AF: 0.0391 AC: 468 AN: 11978 Hom.: 3 Cov.: 0 AF XY: 0.0402 AC XY: 224 AN XY: 5566

Gnomad4 AFR AF: 0.0436

Gnomad4 AMR AF: 0.0633

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00425

Gnomad4 OTH AF: 0.0366

Alfa AF: 0.00110 Hom.: 0

Bravo AF: 0.00369

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

Invitae

Feb 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	1.7
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000092
dbscSNV1_RF	Benign	0.012
SpliceAI score (max)		0.060		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: rs375253952; hg19: chr14-80993331;