rs2292267

Variant names:

• chr5-10263470-G-A
• rs2292267
• NM_012073.5:c.1498+156G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-10263470-G-A
• chr5-10263470-G-C
• chr5-10263470-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012073.5(CCT5):​c.1498+156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,188 control chromosomes in the GnomAD database, including 3,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.16 (3816 hom., cov: 34)
• Consequence: CCT5 NM_012073.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.700
• Publications: 6 publications found

Genes affected

CCT5 (HGNC:1618): (chaperonin containing TCP1 subunit 5) The protein encoded by this gene is a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). This complex consists of two identical stacked rings, each containing eight different proteins. Unfolded polypeptides enter the central cavity of the complex and are folded in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Mutations in this gene cause hereditary sensory and autonomic neuropathy with spastic paraplegia (HSNSP). Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 5 and 13. [provided by RefSeq, Apr 2015]

CCT5 Gene-Disease associations (from GenCC):

• hereditary sensory and autonomic neuropathy with spastic paraplegia

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-10263470-G-A is Benign according to our data. Variant chr5-10263470-G-A is described in ClinVar as [Benign]. Clinvar id is 1228359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT5	NM_012073.5	c.1498+156G>A		intron_variant	Intron 10 of 10	ENST00000280326.9	NP_036205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT5	ENST00000280326.9	c.1498+156G>A		intron_variant	Intron 10 of 10	1	NM_012073.5	ENSP00000280326.4

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23613 AN: 152070 Hom.: 3817 Cov.: 34

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0757

Gnomad ASJ AF: 0.0592

Gnomad EAS AF: 0.0304

Gnomad SAS AF: 0.0666

Gnomad FIN AF: 0.0766

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0507

Gnomad OTH AF: 0.126

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.155 AC: 23638 AN: 152188 Hom.: 3816 Cov.: 34 AF XY: 0.152 AC XY: 11280 AN XY: 74418

African (AFR) AF: 0.415 AC: 17220 AN: 41476

American (AMR) AF: 0.0755 AC: 1155 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0592 AC: 205 AN: 3464

East Asian (EAS) AF: 0.0305 AC: 158 AN: 5184

South Asian (SAS) AF: 0.0654 AC: 316 AN: 4830

European-Finnish (FIN) AF: 0.0766 AC: 812 AN: 10600

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0507 AC: 3450 AN: 68016

Other (OTH) AF: 0.125 AC: 265 AN: 2112

Alfa AF: 0.0767 Hom.: 1750

Bravo AF: 0.167

Asia WGS AF: 0.0810 AC: 283 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.14
DANN	Benign	0.32
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2292267; hg19: chr5-10263582;