11-101948072-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_020802.4(CEP126):c.436C>G(p.Gln146Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,611,840 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (19 hom.)
• Consequence: CEP126 NM_020802.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.30

Genes affected

CEP126 (HGNC:29264): (centrosomal protein 126) Involved in cilium assembly; cytoplasmic microtubule organization; and mitotic spindle organization. Located in centrosome; ciliary base; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007989496).
• BP6: Variant 11-101948072-C-G is Benign according to our data. Variant chr11-101948072-C-G is described in ClinVar as [Benign]. Clinvar id is 774477.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP126	NM_020802.4	c.436C>G	p.Gln146Glu	missense_variant	4/11	ENST00000263468.13
CEP126	NM_001363543.2	c.-844C>G		5_prime_UTR_variant	4/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP126	ENST00000263468.13	c.436C>G	p.Gln146Glu	missense_variant	4/11	1	NM_020802.4	P1
CEP126	ENST00000532529.1	c.79C>G	p.Gln27Glu	missense_variant, NMD_transcript_variant	2/10	5
CEP126	ENST00000670091.1	c.436C>G	p.Gln146Glu	missense_variant, NMD_transcript_variant	4/12
CEP126	ENST00000670318.1	c.436C>G	p.Gln146Glu	missense_variant, NMD_transcript_variant	4/12

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 216 AN: 152120 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00267 AC: 671 AN: 251002 Hom.: 4 AF XY: 0.00330 AC XY: 448 AN XY: 135658

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0123

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.00193

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00208 AC: 3031 AN: 1459602 Hom.: 19 Cov.: 29 AF XY: 0.00240 AC XY: 1746 AN XY: 726136

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.00134

Gnomad4 ASJ exome AF: 0.00123

Gnomad4 EAS exome AF: 0.0000758

Gnomad4 SAS exome AF: 0.0116

Gnomad4 FIN exome AF: 0.000506

Gnomad4 NFE exome AF: 0.00153

Gnomad4 OTH exome AF: 0.00250

GnomAD4 genome AF: 0.00141 AC: 215 AN: 152238 Hom.: 2 Cov.: 32 AF XY: 0.00129 AC XY: 96 AN XY: 74434

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00154

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00157 Hom.: 2

Bravo AF: 0.00115

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.00299 AC: 363

Asia WGS AF: 0.00376 AC: 13 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.29
Cadd	Uncertain	23
Dann	Uncertain	0.99
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.87	D
MetaRNN	Benign	0.0080	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.93	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.20
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Vest4		0.44
MVP		0.51
MPC		0.56
ClinPred		0.034	T
GERP RS		5.4
gMVP		0.20

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: rs142141239; hg19: chr11-101818803; COSMIC: COSV54826171;