dbSNP rs377387784: IFT88:c.-7+746C>T (chr13-20568002-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_175605.5(IFT88):c.21+5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 713,254 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

IFT88
NM_175605.5 splice_region, intron

Scores

Splicing: ADA: 0.001220

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0570

Publications

0 publications found

Variant links:

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

IFT88 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 13-20568002-C-T is Benign according to our data. Variant chr13-20568002-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1585380.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 125 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175605.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IFT88	NM_006531.5	MANE Select	c.-7+746C>T	intron	N/A	NP_006522.2
IFT88	NM_001318493.2		c.21+5C>T	splice_region intron	N/A	NP_001305422.1	Q13099-1
IFT88	NM_001353565.2		c.21+5C>T	splice_region intron	N/A	NP_001340494.1	Q13099-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IFT88	ENST00000351808.10	TSL:1 MANE Select	c.-7+746C>T	intron	N/A	ENSP00000261632.5	Q13099-2
IFT88	ENST00000319980.10	TSL:1	c.21+5C>T	splice_region intron	N/A	ENSP00000323580.6	Q13099-1
IFT88	ENST00000894242.1		c.-138+746C>T	intron	N/A	ENSP00000564301.1

Frequencies

GnomAD3 genomes

AF:

0.000825

AC:

125

AN:

151534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000385

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00101

AC:

150

AN:

149048

AF XY:

0.000899

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00353

Gnomad EAS exome

AF:

0.0000897

Gnomad FIN exome

AF:

0.000351

Gnomad NFE exome

AF:

0.00163

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00123

AC:

690

AN:

561612

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

391

AN XY:

303370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15794

American (AMR)

AF:

0.000375

AC:

AN:

34694

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

20010

East Asian (EAS)

AF:

0.00

AC:

AN:

32102

South Asian (SAS)

AF:

0.000223

AC:

AN:

62752

European-Finnish (FIN)

AF:

0.000357

AC:

AN:

44770

Middle Eastern (MID)

AF:

0.00246

AC:

AN:

4068

European-Non Finnish (NFE)

AF:

0.00167

AC:

529

AN:

316766

Other (OTH)

AF:

0.00108

AC:

AN:

30656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000824

AC:

125

AN:

151642

Hom.:

Cov.:

AF XY:

0.000675

AC XY:

AN XY:

74070

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41342

American (AMR)

AF:

0.000263

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5158

South Asian (SAS)

AF:

0.000415

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000385

AC:

AN:

10390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00141

AC:

AN:

67910

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000876

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.5

(source)

DANN

Benign

0.37

PhyloP100

-0.057

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0012

dbscSNV1_RF

Benign

0.036

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over