14-104883085-G-A

Position:

• chr14-104883085-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001112726.3(CEP170B):​c.628G>A​(p.Ala210Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,417,182 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A210V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.000015 (1 hom.)
• Consequence: CEP170B NM_001112726.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.414

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0749284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP170B	NM_001112726.3	c.628G>A	p.Ala210Thr	missense_variant	8/19	ENST00000414716.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP170B	ENST00000414716.8	c.628G>A	p.Ala210Thr	missense_variant	8/19	1	NM_001112726.3	P1
CEP170B	ENST00000556508.5	c.418G>A	p.Ala140Thr	missense_variant	7/18	5

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.0000148 AC: 21 AN: 1417182 Hom.: 1 Cov.: 39 AF XY: 0.0000228 AC XY: 16 AN XY: 701298

Gnomad4 AFR exome AF: 0.000214

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000236

Gnomad4 EAS exome AF: 0.0000265

Gnomad4 SAS exome AF: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000275

Gnomad4 OTH exome AF: 0.0000510

GnomAD4 genome Cov.: 28

Alfa AF: 0.0000303 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.628G>A (p.A210T) alteration is located in exon 8 (coding exon 7) of the CEP170B gene. This alteration results from a G to A substitution at nucleotide position 628, causing the alanine (A) at amino acid position 210 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.9
DANN	Benign	0.96
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.50	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.075	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.010
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.56	T;T;T
Polyphen		0.066	.;B;.
Vest4		0.086
MutPred		0.22		.;Gain of catalytic residue at R209 (P = 0.0081);.;
MVP		0.16
MPC		0.17
ClinPred		0.019	T
GERP RS		-1.3
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs1194840601; hg19: chr14-105349422;