rs891819

Variant names:

• chr2-165886830-G-A
• rs891819
• NM_024753.5:c.3459+1449C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

TTC21B Gene-Disease associations (from GenCC):

• nephronophthisis 12

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• asphyxiating thoracic dystrophy 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nephronophthisis 2

  Inheritance: AR 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024753.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC21B	NM_024753.5	MANE Select	c.3459+1449C>T		intron	N/A	NP_079029.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC21B	ENST00000243344.8	TSL:1 MANE Select	c.3459+1449C>T		intron	N/A	ENSP00000243344.7
	TTC21B	ENST00000679840.1		c.3459+1449C>T		intron	N/A	ENSP00000505248.1
	TTC21B	ENST00000679799.1		c.3459+1449C>T		intron	N/A	ENSP00000505208.1

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

African (AFR) AF: 0.222 AC: 9208 AN: 41486

American (AMR) AF: 0.251 AC: 3834 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3470

East Asian (EAS) AF: 0.344 AC: 1780 AN: 5168

South Asian (SAS) AF: 0.188 AC: 908 AN: 4820

European-Finnish (FIN) AF: 0.271 AC: 2855 AN: 10548

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.157 AC: 10685 AN: 67992

Other (OTH) AF: 0.167 AC: 352 AN: 2104

Alfa AF: 0.169 Hom.: 1989

Bravo AF: 0.198

Asia WGS AF: 0.259 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.38
PhyloP100		0.34
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: rs891819; hg19: chr2-166743340;