13-20631001-A-T

Variant names:

• chr13-20631001-A-T
• rs1329519
• NM_006531.5:c.1300-15A>T

Variant summary

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

The NM_006531.5(IFT88):​c.1300-15A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 1,462,846 control chromosomes in the GnomAD database, including 400,386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (37816 hom., cov: 31)
  • Exomes 𝑓: 0.74 (362570 hom.)
• Consequence: IFT88 NM_006531.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.109
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 13-20631001-A-T is Benign according to our data. Variant chr13-20631001-A-T is described in ClinVar as Benign. ClinVar VariationId is 402966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT88	NM_006531.5	MANE Select	c.1300-15A>T		intron	N/A	NP_006522.2
	IFT88	NM_001318493.2		c.1327-15A>T		intron	N/A	NP_001305422.1
	IFT88	NM_001353565.2		c.1327-15A>T		intron	N/A	NP_001340494.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT88	ENST00000351808.10	TSL:1 MANE Select	c.1300-15A>T		intron	N/A	ENSP00000261632.5
	IFT88	ENST00000319980.10	TSL:1	c.1327-15A>T		intron	N/A	ENSP00000323580.6
	IFT88	ENST00000537103.2	TSL:5	c.709-15A>T		intron	N/A	ENSP00000437719.2

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105641 AN: 151826 Hom.: 37800 Cov.: 31

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.718

GnomAD2 exomes AF: 0.770 AC: 192903 AN: 250504 AF XY: 0.774

Gnomad AFR exome AF: 0.531

Gnomad AMR exome AF: 0.854

Gnomad ASJ exome AF: 0.694

Gnomad EAS exome AF: 0.997

Gnomad FIN exome AF: 0.748

Gnomad NFE exome AF: 0.725

Gnomad OTH exome AF: 0.740

GnomAD4 exome AF: 0.740 AC: 969548 AN: 1310902 Hom.: 362570 Cov.: 19 AF XY: 0.745 AC XY: 492163 AN XY: 660512

African (AFR) AF: 0.519 AC: 16044 AN: 30894

American (AMR) AF: 0.843 AC: 37520 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 17236 AN: 25230

East Asian (EAS) AF: 0.998 AC: 38738 AN: 38830

South Asian (SAS) AF: 0.871 AC: 72080 AN: 82764

European-Finnish (FIN) AF: 0.745 AC: 39602 AN: 53134

Middle Eastern (MID) AF: 0.768 AC: 4201 AN: 5470

European-Non Finnish (NFE) AF: 0.722 AC: 703499 AN: 974830

Other (OTH) AF: 0.735 AC: 40628 AN: 55266

GnomAD4 genome AF: 0.696 AC: 105703 AN: 151944 Hom.: 37816 Cov.: 31 AF XY: 0.705 AC XY: 52309 AN XY: 74240

African (AFR) AF: 0.540 AC: 22342 AN: 41372

American (AMR) AF: 0.779 AC: 11899 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2383 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5158 AN: 5178

South Asian (SAS) AF: 0.885 AC: 4273 AN: 4828

European-Finnish (FIN) AF: 0.746 AC: 7858 AN: 10530

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49376 AN: 67968

Other (OTH) AF: 0.719 AC: 1518 AN: 2110

Alfa AF: 0.672 Hom.: 4398

Bravo AF: 0.688

Asia WGS AF: 0.915 AC: 3179 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.4
DANN	Benign	0.79
PhyloP100		0.11
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: rs1329519; hg19: chr13-21205140;