14-104883083-G-A

Position:

• chr14-104883083-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001112726.3(CEP170B):​c.626G>A​(p.Arg209His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000683 in 1,565,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: CEP170B NM_001112726.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.875

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034406602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP170B	NM_001112726.3	c.626G>A	p.Arg209His	missense_variant	8/19	ENST00000414716.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP170B	ENST00000414716.8	c.626G>A	p.Arg209His	missense_variant	8/19	1	NM_001112726.3	P1
CEP170B	ENST00000556508.5	c.416G>A	p.Arg139His	missense_variant	7/18	5

Frequencies

GnomAD3 genomes AF: 0.0000858 AC: 13 AN: 151474 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000971

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000867

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000884

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000133 AC: 24 AN: 180076 Hom.: 0 AF XY: 0.000111 AC XY: 11 AN XY: 98980

Gnomad AFR exome AF: 0.000306

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00126

Gnomad EAS exome AF: 0.0000723

Gnomad SAS exome AF: 0.0000793

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000903

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000665 AC: 94 AN: 1414436 Hom.: 0 Cov.: 39 AF XY: 0.0000729 AC XY: 51 AN XY: 699676

Gnomad4 AFR exome AF: 0.0000921

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000868

Gnomad4 EAS exome AF: 0.0000531

Gnomad4 SAS exome AF: 0.000110

Gnomad4 FIN exome AF: 0.0000236

Gnomad4 NFE exome AF: 0.0000476

Gnomad4 OTH exome AF: 0.0000681

GnomAD4 genome AF: 0.0000858 AC: 13 AN: 151474 Hom.: 0 Cov.: 28 AF XY: 0.0000811 AC XY: 6 AN XY: 73938

Gnomad4 AFR AF: 0.0000971

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000867

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000884

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000226 Hom.: 0

Bravo AF: 0.0000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000123 AC: 1

ExAC AF: 0.0000764 AC: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.034	T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.036
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.72	.;P;.
Vest4		0.28
MVP		0.23
MPC		0.28
ClinPred		0.016	T
GERP RS		2.2
gMVP		0.15

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: rs370815644; hg19: chr14-105349420;