NM_006531.5:c.1387-2959G>A

Variant names:

• chr13-20635373-G-A
• rs7326068
• NM_006531.5:c.1387-2959G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006531.5(IFT88):​c.1387-2959G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,082 control chromosomes in the GnomAD database, including 5,427 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (5427 hom., cov: 30)
• Consequence: IFT88 NM_006531.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT88	NM_006531.5	c.1387-2959G>A		intron_variant	Intron 16 of 25	ENST00000351808.10	NP_006522.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT88	ENST00000351808.10	c.1387-2959G>A		intron_variant	Intron 16 of 25	1	NM_006531.5	ENSP00000261632.5
IFT88	ENST00000319980.10	c.1414-2959G>A		intron_variant	Intron 18 of 27	1		ENSP00000323580.6
IFT88	ENST00000537103.2	c.796-2959G>A		intron_variant	Intron 9 of 10	5		ENSP00000437719.2
IFT88	ENST00000482172.5	n.276+4271G>A		intron_variant	Intron 3 of 9	3

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34883 AN: 151964 Hom.: 5414 Cov.: 30

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.230 AC: 34906 AN: 152082 Hom.: 5427 Cov.: 30 AF XY: 0.242 AC XY: 17953 AN XY: 74318

African (AFR) AF: 0.127 AC: 5269 AN: 41502

American (AMR) AF: 0.391 AC: 5968 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3470

East Asian (EAS) AF: 0.699 AC: 3616 AN: 5172

South Asian (SAS) AF: 0.462 AC: 2223 AN: 4814

European-Finnish (FIN) AF: 0.269 AC: 2837 AN: 10556

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.203 AC: 13797 AN: 67978

Other (OTH) AF: 0.205 AC: 433 AN: 2108

Alfa AF: 0.228 Hom.: 10045

Bravo AF: 0.234

Asia WGS AF: 0.578 AC: 2008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.69
DANN	Benign	0.26
PhyloP100		-0.15
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: rs7326068; hg19: chr13-21209512;