Genetic Variant CEP126:c.249-7A>C (chr11-101944258-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020802.4(CEP126):c.249-7A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,560,540 control chromosomes in the GnomAD database, including 17 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 6 hom. )

Consequence

CEP126
NM_020802.4 splice_region, intron

Scores

Splicing: ADA: 0.0001475

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.79

Variant links:

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]

CEP126 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-101944258-A-C is Benign according to our data. Variant chr11-101944258-A-C is described in ClinVar as [Benign]. Clinvar id is 786210.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00586 (892/152172) while in subpopulation AFR AF= 0.0204 (846/41538). AF 95% confidence interval is 0.0192. There are 11 homozygotes in gnomad4. There are 445 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP126	NM_020802.4 link	c.249-7A>C		splice_region_variant, intron_variant	Intron 2 of 10	ENST00000263468.13	NP_065853.3	Q9P2H0
CEP126	NM_001363543.2 link	c.-1031-7A>C		splice_region_variant, intron_variant	Intron 2 of 11		NP_001350472.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CEP126	ENST00000263468.13 link	c.249-7A>C	splice_region_variant, intron_variant	Intron 2 of 10	1	NM_020802.4	ENSP00000263468.8	Q9P2H0
CEP126	ENST00000670091.1 link	n.249-7A>C	splice_region_variant, intron_variant	Intron 2 of 11			ENSP00000499679.1	A0A590UK33
CEP126	ENST00000670318.1 link	n.249-7A>C	splice_region_variant, intron_variant	Intron 2 of 11			ENSP00000499404.1	A0A590UJH0
CEP126	ENST00000532529.1 link	n.-119A>C	upstream_gene_variant		5		ENSP00000433643.1	H0YDI0

Frequencies

GnomAD3 genomes

AF:

0.00579

AC:

880

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00139

AC:

286

AN:

205514

Hom.:

AF XY:

0.000980

AC XY:

110

AN XY:

112274

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.000912

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:

0.0000802

Gnomad OTH exome

AF:

0.000429

GnomAD4 exome

AF:

0.000540

AC:

760

AN:

1408368

Hom.:

Cov.:

AF XY:

0.000452

AC XY:

316

AN XY:

699108

show subpopulations

Gnomad4 AFR exome

AF:

0.0199

Gnomad4 AMR exome

AF:

0.00118

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000400

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000457

Gnomad4 OTH exome

AF:

0.00133

GnomAD4 genome

AF:

0.00586

AC:

892

AN:

152172

Hom.:

Cov.:

AF XY:

0.00598

AC XY:

445

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0204

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00295

Hom.:

Bravo

AF:

0.00659

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 16, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.0020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over