17-81208867-A-G

Position:

• chr17-81208867-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014984.4(CEP131):​c.272+61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 1,326,124 control chromosomes in the GnomAD database, including 597,395 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.92 (65215 hom., cov: 31)
  • Exomes 𝑓: 0.95 (532180 hom.)
• Consequence: CEP131 NM_014984.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

Genes affected

CEP131 (HGNC:29511): (centrosomal protein 131) Enables protein homodimerization activity. Involved in several processes, including intraciliary transport involved in cilium assembly; protein localization to centrosome; and regulation of centrosome duplication. Located in several cellular components, including ciliary transition zone; intercellular bridge; and microtubule organizing center. Colocalizes with centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP131	NM_014984.4	c.272+61T>C		intron_variant		ENST00000450824.7	NP_055799.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP131	ENST00000450824.7	c.272+61T>C		intron_variant		1	NM_014984.4	ENSP00000393583	P3
CEP131	ENST00000269392.8	c.272+61T>C		intron_variant		1		ENSP00000269392	A2
CEP131	ENST00000575907.5	c.272+61T>C		intron_variant		1		ENSP00000459733	A2
CEP131	ENST00000374782.7	c.272+61T>C		intron_variant		5		ENSP00000363914	A2

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140561 AN: 152044 Hom.: 65170 Cov.: 31

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.941

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.966

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.962

Gnomad OTH AF: 0.928

GnomAD4 exome AF: 0.952 AC: 1117166 AN: 1173962 Hom.: 532180 AF XY: 0.950 AC XY: 566126 AN XY: 595942

Gnomad4 AFR exome AF: 0.847

Gnomad4 AMR exome AF: 0.953

Gnomad4 ASJ exome AF: 0.969

Gnomad4 EAS exome AF: 0.872

Gnomad4 SAS exome AF: 0.895

Gnomad4 FIN exome AF: 0.967

Gnomad4 NFE exome AF: 0.963

Gnomad4 OTH exome AF: 0.941

GnomAD4 genome AF: 0.924 AC: 140662 AN: 152162 Hom.: 65215 Cov.: 31 AF XY: 0.924 AC XY: 68760 AN XY: 74392

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.947

Gnomad4 ASJ AF: 0.966

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.897

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.962

Gnomad4 OTH AF: 0.929

Alfa AF: 0.943 Hom.: 8423

Bravo AF: 0.919

Asia WGS AF: 0.872 AC: 3033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.21
DANN	Benign	0.42

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: rs9896314; hg19: chr17-79182667;