rs140387257

Variant names:

• chr11-101944258-A-C
• rs140387257
• NM_020802.4:c.249-7A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020802.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP126	NM_020802.4	MANE Select	c.249-7A>C		splice_region intron	N/A	NP_065853.3	Q9P2H0
	CEP126	NM_001363543.2		c.-1031-7A>C		splice_region intron	N/A	NP_001350472.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP126	ENST00000263468.13	TSL:1 MANE Select	c.249-7A>C		splice_region intron	N/A	ENSP00000263468.8	Q9P2H0
	CEP126	ENST00000931861.1		c.249-7A>C		splice_region intron	N/A	ENSP00000601920.1
	CEP126	ENST00000670091.1		n.249-7A>C		splice_region intron	N/A	ENSP00000499679.1	A0A590UK33

Frequencies

GnomAD3 genomes AF: 0.00579 AC: 880 AN: 152054 Hom.: 10 Cov.: 32

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

GnomAD2 exomes AF: 0.00139 AC: 286 AN: 205514 AF XY: 0.000980

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 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.: 6 Cov.: 30 AF XY: 0.000452 AC XY: 316 AN XY: 699108

African (AFR) AF: 0.0199 AC: 590 AN: 29700

American (AMR) AF: 0.00118 AC: 38 AN: 32196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24674

East Asian (EAS) AF: 0.00 AC: 0 AN: 36972

South Asian (SAS) AF: 0.0000400 AC: 3 AN: 74924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52838

Middle Eastern (MID) AF: 0.000377 AC: 2 AN: 5312

European-Non Finnish (NFE) AF: 0.0000457 AC: 50 AN: 1093676

Other (OTH) AF: 0.00133 AC: 77 AN: 58076

GnomAD4 genome AF: 0.00586 AC: 892 AN: 152172 Hom.: 11 Cov.: 32 AF XY: 0.00598 AC XY: 445 AN XY: 74424

African (AFR) AF: 0.0204 AC: 846 AN: 41538

American (AMR) AF: 0.00190 AC: 29 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67946

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00274 Hom.: 3

Bravo AF: 0.00659

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.57
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs140387257; hg19: chr11-101814989;