11-93730221-C-T

Variant names:

• chr11-93730221-C-T
• rs139948226
• ENST00000526015.5:n.*672G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_033395.2(CEP295):​c.7768-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000489 in 1,551,222 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: CEP295 NM_033395.2 intron
• Scores: Splicing: ADA: 0.00001562
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.538
• Publications: 0 publications found

Genes affected

TAF1D (HGNC:28759): (TATA-box binding protein associated factor, RNA polymerase I subunit D) TAF1D is a member of the SL1 complex, which includes TBP (MIM 600075) and TAF1A (MIM 604903), TAF1B (MIM 604904), and TAF1C (MIM 604905), and plays a role in RNA polymerase I transcription (Wang et al., 2004 [PubMed 15520167]; Gorski et al., 2007 [PubMed 17318177]).[supplied by OMIM, Jun 2009]

CEP295 (HGNC:29366): (centrosomal protein 295) Enables microtubule binding activity. Involved in several processes, including centriole replication; positive regulation of protein acetylation; and regulation of centrosome duplication. Located in cytosol; microtubule cytoskeleton; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-93730221-C-T is Benign according to our data. Variant chr11-93730221-C-T is described in ClinVar as [Benign]. Clinvar id is 710124.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP295	NM_033395.2	c.7768-10C>T		intron_variant	Intron 29 of 29	ENST00000325212.11	NP_203753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP295	ENST00000325212.11	c.7768-10C>T		intron_variant	Intron 29 of 29	2	NM_033395.2	ENSP00000316681.6

Frequencies

GnomAD3 genomes AF: 0.00265 AC: 403 AN: 152108 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00939

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000549 AC: 86 AN: 156544 AF XY: 0.000459

Gnomad AFR exome AF: 0.00833

Gnomad AMR exome AF: 0.000772

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000228

GnomAD4 exome AF: 0.000254 AC: 355 AN: 1398996 Hom.: 0 Cov.: 33 AF XY: 0.000226 AC XY: 156 AN XY: 690012

African (AFR) AF: 0.00963 AC: 304 AN: 31566

American (AMR) AF: 0.000785 AC: 28 AN: 35658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25166

East Asian (EAS) AF: 0.00 AC: 0 AN: 35690

South Asian (SAS) AF: 0.00 AC: 0 AN: 79220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49272

Middle Eastern (MID) AF: 0.000888 AC: 5 AN: 5630

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078824

Other (OTH) AF: 0.000293 AC: 17 AN: 57970

GnomAD4 genome AF: 0.00265 AC: 404 AN: 152226 Hom.: 2 Cov.: 32 AF XY: 0.00255 AC XY: 190 AN XY: 74412

African (AFR) AF: 0.00941 AC: 391 AN: 41558

American (AMR) AF: 0.000720 AC: 11 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00141 Hom.: 0

Bravo AF: 0.00320

Asia WGS AF: 0.000578 AC: 2 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 02, 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	-0.80
CADD	Benign	8.4
DANN	Benign	0.71
PhyloP100		-0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
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: rs139948226; hg19: chr11-93463387;