chr8-67149947-CTTTTTTTTTTTTT-C

Variant names:

• chr8-67149947-CTTTTTTTTTTTTT-C
• rs11296619
• NM_001382391.1:c.2128+24_2128+36delTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001364869.1(CSPP1):​c.2194+24_2194+36delTTTTTTTTTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.00000572 in 1,049,696 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: CSPP1 NM_001364869.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.17
• Publications: 0 publications found

Genes affected

CSPP1 (HGNC:26193): (centrosome and spindle pole associated protein 1) This gene encodes a centrosome and spindle pole associated protein. The encoded protein plays a role in cell-cycle progression and spindle organization, regulates cytokinesis, interacts with Nephrocystin 8 and is required for cilia formation. Mutations in this gene result in primary cilia abnormalities and classical Joubert syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

CSPP1 Gene-Disease associations (from GenCC):

• Joubert syndrome 21

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with Jeune asphyxiating thoracic dystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 8-67149947-CTTTTTTTTTTTTT-C is Benign according to our data. Variant chr8-67149947-CTTTTTTTTTTTTT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2185736.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364869.1. 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
	CSPP1	NM_001382391.1	MANE Select	c.2128+24_2128+36delTTTTTTTTTTTTT		intron	N/A	NP_001369320.1
	CSPP1	NM_001364869.1		c.2194+24_2194+36delTTTTTTTTTTTTT		intron	N/A	NP_001351798.1
	CSPP1	NM_024790.7		c.2113+24_2113+36delTTTTTTTTTTTTT		intron	N/A	NP_079066.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSPP1	ENST00000678616.1	MANE Select	c.2128+13_2128+25delTTTTTTTTTTTTT		intron	N/A	ENSP00000504733.1
	CSPP1	ENST00000262210.11	TSL:1	c.2194+13_2194+25delTTTTTTTTTTTTT		intron	N/A	ENSP00000262210.6
	CSPP1	ENST00000519668.1	TSL:1	c.1079-4076_1079-4064delTTTTTTTTTTTTT		intron	N/A	ENSP00000430092.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000572 AC: 6 AN: 1049696 Hom.: 0 AF XY: 0.00000579 AC XY: 3 AN XY: 517928

African (AFR) AF: 0.000136 AC: 3 AN: 22100

American (AMR) AF: 0.00 AC: 0 AN: 17998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15356

East Asian (EAS) AF: 0.00 AC: 0 AN: 29252

South Asian (SAS) AF: 0.00 AC: 0 AN: 43176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3248

European-Non Finnish (NFE) AF: 0.00000357 AC: 3 AN: 839220

Other (OTH) AF: 0.00 AC: 0 AN: 43090

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Joubert syndrome 21 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11296619; hg19: chr8-68062182;