ENST00000319980:c.-195A>G

Variant names:

• chr13-20567683-A-G
• rs9552244
• ENST00000319980.10:c.-195A>G

Variant summary

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

The ENST00000319980.10(IFT88):​c.-195A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0861 in 1,142,676 control chromosomes in the GnomAD database, including 5,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (901 hom., cov: 33)
  • Exomes 𝑓: 0.085 (4773 hom.)
• Consequence: IFT88 ENST00000319980.10 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.134
• Publications: 5 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=-0.8).
• BP6: Variant 13-20567683-A-G is Benign according to our data. Variant chr13-20567683-A-G is described in ClinVar as Benign. ClinVar VariationId is 1257994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000319980.10. 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+427A>G		intron	N/A	NP_006522.2
	IFT88	NM_001318493.2		c.-294A>G		5_prime_UTR	Exon 2 of 27	NP_001305422.1	Q13099-1
	IFT88	NM_001353566.2		c.-186A>G		5_prime_UTR	Exon 2 of 28	NP_001340495.1	Q13099-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT88	ENST00000319980.10	TSL:1	c.-195A>G		5_prime_UTR	Exon 2 of 28	ENSP00000323580.6	Q13099-1
	IFT88	ENST00000351808.10	TSL:1 MANE Select	c.-7+427A>G		intron	N/A	ENSP00000261632.5	Q13099-2
	IFT88	ENST00000894245.1		c.-321A>G		5_prime_UTR	Exon 1 of 26	ENSP00000564304.1

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14116 AN: 152166 Hom.: 903 Cov.: 33

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.0936

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0904

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0827

GnomAD4 exome AF: 0.0851 AC: 84257 AN: 990392 Hom.: 4773 Cov.: 16 AF XY: 0.0846 AC XY: 39490 AN XY: 466742

African (AFR) AF: 0.0838 AC: 1801 AN: 21502

American (AMR) AF: 0.111 AC: 892 AN: 8062

Ashkenazi Jewish (ASJ) AF: 0.0449 AC: 519 AN: 11552

East Asian (EAS) AF: 0.374 AC: 7082 AN: 18958

South Asian (SAS) AF: 0.141 AC: 3103 AN: 21970

European-Finnish (FIN) AF: 0.0802 AC: 869 AN: 10836

Middle Eastern (MID) AF: 0.0810 AC: 195 AN: 2406

European-Non Finnish (NFE) AF: 0.0770 AC: 66019 AN: 857262

Other (OTH) AF: 0.0998 AC: 3777 AN: 37844

GnomAD4 genome AF: 0.0927 AC: 14112 AN: 152284 Hom.: 901 Cov.: 33 AF XY: 0.0959 AC XY: 7144 AN XY: 74468

African (AFR) AF: 0.0872 AC: 3624 AN: 41554

American (AMR) AF: 0.0935 AC: 1431 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0479 AC: 166 AN: 3468

East Asian (EAS) AF: 0.382 AC: 1977 AN: 5172

South Asian (SAS) AF: 0.149 AC: 718 AN: 4832

European-Finnish (FIN) AF: 0.0904 AC: 959 AN: 10606

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0733 AC: 4987 AN: 68032

Other (OTH) AF: 0.0833 AC: 176 AN: 2114

Alfa AF: 0.0838 Hom.: 1189

Bravo AF: 0.0934

Asia WGS AF: 0.255 AC: 886 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.0
DANN	Benign	0.75
PhyloP100		0.13
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs9552244; hg19: chr13-21141822;