chr2-165884848-G-A

Position:

• chr2-165884848-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.3460-830C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,034 control chromosomes in the GnomAD database, including 16,037 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 0.45 (16037 hom., cov: 33)
• Consequence: TTC21B NM_024753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC21B	NM_024753.5	c.3460-830C>T		intron_variant		ENST00000243344.8	NP_079029.3
TTC21B	XM_017004967.2	c.3460-830C>T		intron_variant			XP_016860456.1
TTC21B	XM_047445870.1	c.2806-830C>T		intron_variant			XP_047301826.1
TTC21B	XM_011511871.4	c.2710-830C>T		intron_variant			XP_011510173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC21B	ENST00000243344.8	c.3460-830C>T		intron_variant		1	NM_024753.5	ENSP00000243344.7

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68894 AN: 151918 Hom.: 16023 Cov.: 33

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.454 AC: 68953 AN: 152034 Hom.: 16037 Cov.: 33 AF XY: 0.458 AC XY: 34022 AN XY: 74312

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.473

Alfa AF: 0.490 Hom.: 18024

Bravo AF: 0.451

Asia WGS AF: 0.448 AC: 1557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.1
DANN	Benign	0.60

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: rs9332423; hg19: chr2-166741358;