NM_001112726.3:c.594A>T

Variant names:

• chr14-104883051-A-T
• rs2028414
• NM_001112726.3:c.594A>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001112726.3(CEP170B):​c.594A>T​(p.Pro198Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 151,256 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000040 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0000073 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEP170B NM_001112726.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

Genes affected

CEP170B (HGNC:20362): (centrosomal protein 170B) Predicted to be located in cytoplasm and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP7: Synonymous conserved (PhyloP=-1.84 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP170B	NM_001112726.3	c.594A>T	p.Pro198Pro	synonymous_variant	Exon 8 of 19	ENST00000414716.8	NP_001106197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP170B	ENST00000414716.8	c.594A>T	p.Pro198Pro	synonymous_variant	Exon 8 of 19	1	NM_001112726.3	ENSP00000404151.2
CEP170B	ENST00000556508.5	c.384A>T	p.Pro128Pro	synonymous_variant	Exon 7 of 18	5		ENSP00000451249.1

Frequencies

GnomAD3 genomes AF: 0.0000397 AC: 6 AN: 151138 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000731

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.000483

GnomAD3 exomes AF: 0.0000136 AC: 2 AN: 146532 Hom.: 0 AF XY: 0.0000250 AC XY: 2 AN XY: 80140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000402

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000166

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000725 AC: 10 AN: 1378382 Hom.: 0 Cov.: 64 AF XY: 0.00000884 AC XY: 6 AN XY: 678364

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000653

Gnomad4 OTH exome AF: 0.0000175

GnomAD4 genome AF: 0.0000397 AC: 6 AN: 151256 Hom.: 0 Cov.: 27 AF XY: 0.0000542 AC XY: 4 AN XY: 73850

Gnomad4 AFR AF: 0.0000729

Gnomad4 AMR AF: 0.0000657

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.000478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.41
DANN	Benign	0.56

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: rs2028414; hg19: chr14-105349388;