rs1402769479

Variant names:

• chr13-20568013-TA-T
• rs1402769479
• NM_006531.5:c.-7+765delA

Your query was ambiguous. Multiple possible variants found:

• chr13-20568013-TA-T
• chr13-20568013-TA-TAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006531.5(IFT88):​c.-7+765delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000178 in 561,326 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: IFT88 NM_006531.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• Publications: 0 publications found

Genes affected

IFT88 (HGNC:20606): (intraflagellar transport 88) This gene encodes a member of the tetratrico peptide repeat (TPR) family. The encoded protein is involved in cilium biogenesis. Mutations of a similar gene in mouse can cause polycystic kidney disease. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2017]

IFT88 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006531.5. 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
	IFT88	NM_006531.5	MANE Select	c.-7+765delA		intron	N/A	NP_006522.2
	IFT88	NM_001318493.2		c.21+24delA		intron	N/A	NP_001305422.1	Q13099-1
	IFT88	NM_001353565.2		c.21+24delA		intron	N/A	NP_001340494.1	Q13099-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT88	ENST00000351808.10	TSL:1 MANE Select	c.-7+758delA		intron	N/A	ENSP00000261632.5	Q13099-2
	IFT88	ENST00000319980.10	TSL:1	c.21+17delA		intron	N/A	ENSP00000323580.6	Q13099-1
	IFT88	ENST00000894242.1		c.-138+758delA		intron	N/A	ENSP00000564301.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000178 AC: 1 AN: 561326 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 303264

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15784

American (AMR) AF: 0.00 AC: 0 AN: 34644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19994

East Asian (EAS) AF: 0.00 AC: 0 AN: 32094

South Asian (SAS) AF: 0.00 AC: 0 AN: 62720

European-Finnish (FIN) AF: 0.0000224 AC: 1 AN: 44678

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4068

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 316696

Other (OTH) AF: 0.00 AC: 0 AN: 30648

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.38

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: rs1402769479; hg19: chr13-21142152; COSMIC: COSV100179491; COSMIC: COSV100179491;