rs891819

chr2-165886830-G-A

Variant summary

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

The NM_024753.5(TTC21B):c.3459+1449C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,076 control chromosomes in the GnomAD database, including 3,203 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 0.20 (3203 hom., cov: 32)
• Consequence: TTC21B NM_024753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338

Genes affected

TTC21B (HGNC:25660): (tetratricopeptide repeat domain 21B) This gene encodes a member of TTC21 family, containing several tetratricopeptide repeat (TPR) domains. This protein is localized to the cilium axoneme, and may play a role in retrograde intraflagellar transport in cilia. Mutations in this gene are associated with various ciliopathies, nephronophthisis 12, and asphyxiating thoracic dystrophy 4. [provided by RefSeq, Oct 2011]

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 = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC21B	NM_024753.5	c.3459+1449C>T		intron_variant		ENST00000243344.8
TTC21B	XM_011511871.4	c.2709+1449C>T		intron_variant
TTC21B	XM_017004967.2	c.3459+1449C>T		intron_variant
TTC21B	XM_047445870.1	c.2805+1449C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC21B	ENST00000243344.8	c.3459+1449C>T		intron_variant		1	NM_024753.5	P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30043 AN: 151958 Hom.: 3197 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.198 AC: 30093 AN: 152076 Hom.: 3203 Cov.: 32 AF XY: 0.204 AC XY: 15189 AN XY: 74340

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.167

Alfa AF: 0.161 Hom.: 1245

Bravo AF: 0.198

Asia WGS AF: 0.259 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.9
Dann	Benign	0.38

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: rs891819; hg19: chr2-166743340;