rs17700521

chr14-88849531-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144596.4(TTC8):c.625-3440C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,880 control chromosomes in the GnomAD database, including 3,828 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 0.21 (3828 hom., cov: 32)
• Consequence: TTC8 NM_144596.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189

Genes affected

TTC8 (HGNC:20087): (tetratricopeptide repeat domain 8) This gene encodes a protein that has been directly linked to Bardet-Biedl syndrome. The primary features of this syndrome include retinal dystrophy, obesity, polydactyly, renal abnormalities and learning disabilities. Experimentation in non-human eukaryotes suggests that this gene is expressed in ciliated cells and that it is involved in the formation of cilia. A mutation in this gene has also been implicated in nonsyndromic retinitis pigmentosa. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC8	NM_144596.4	c.625-3440C>G		intron_variant		ENST00000380656.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC8	ENST00000380656.7	c.625-3440C>G		intron_variant		2	NM_144596.4

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31708 AN: 151764 Hom.: 3820 Cov.: 32

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.209 AC: 31740 AN: 151880 Hom.: 3828 Cov.: 32 AF XY: 0.207 AC XY: 15386 AN XY: 74214

Gnomad4 AFR AF: 0.0931

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.190

Alfa AF: 0.233 Hom.: 545

Bravo AF: 0.200

Asia WGS AF: 0.235 AC: 815 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.8
Dann	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs17700521; hg19: chr14-89315875;