13-20574472-C-T

Variant names:

• chr13-20574472-C-T
• rs770914774
• NM_006531.5:c.87C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001353579.2(IFT88):​c.-477C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,419,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: IFT88 NM_001353579.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.08
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 13-20574472-C-T is Benign according to our data. Variant chr13-20574472-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1643566.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 18 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353579.2. 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.87C>T	p.Ile29Ile	synonymous	Exon 2 of 26	NP_006522.2
	IFT88	NM_001353579.2		c.-477C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 25	NP_001340508.1
	IFT88	NM_001318493.2		c.114C>T	p.Ile38Ile	synonymous	Exon 3 of 27	NP_001305422.1	Q13099-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT88	ENST00000351808.10	TSL:1 MANE Select	c.87C>T	p.Ile29Ile	synonymous	Exon 2 of 26	ENSP00000261632.5	Q13099-2
	IFT88	ENST00000319980.10	TSL:1	c.114C>T	p.Ile38Ile	synonymous	Exon 4 of 28	ENSP00000323580.6	Q13099-1
	IFT88	ENST00000894242.1		c.87C>T	p.Ile29Ile	synonymous	Exon 3 of 27	ENSP00000564301.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000122 AC: 3 AN: 246772 AF XY: 0.00000750

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000127 AC: 18 AN: 1419984 Hom.: 0 Cov.: 23 AF XY: 0.0000141 AC XY: 10 AN XY: 708682

African (AFR) AF: 0.00 AC: 0 AN: 32398

American (AMR) AF: 0.00 AC: 0 AN: 43898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25776

East Asian (EAS) AF: 0.00 AC: 0 AN: 39106

South Asian (SAS) AF: 0.0000239 AC: 2 AN: 83812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53158

Middle Eastern (MID) AF: 0.000529 AC: 3 AN: 5670

European-Non Finnish (NFE) AF: 0.0000111 AC: 12 AN: 1077324

Other (OTH) AF: 0.0000170 AC: 1 AN: 58842

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.021
DANN	Benign	0.76
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs770914774; hg19: chr13-21148611; COSMIC: COSV60673762;