rs5762448

Positions:

• chr22-28012456-A-C

Variant summary

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

The NM_001145418.2(TTC28):​c.4218+1792T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,104 control chromosomes in the GnomAD database, including 4,004 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 (4004 hom., cov: 32)
• Consequence: TTC28 NM_001145418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

Genes affected

TTC28 (HGNC:29179): (tetratricopeptide repeat domain 28) Enables kinase binding activity. Involved in regulation of mitotic cell cycle. Located in midbody. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC28	NM_001145418.2	c.4218+1792T>G		intron_variant		ENST00000397906.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC28	ENST00000397906.7	c.4218+1792T>G		intron_variant		1	NM_001145418.2	P1
TTC28	ENST00000612946.4	c.3837+1792T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32458 AN: 151986 Hom.: 4000 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.214 AC: 32491 AN: 152104 Hom.: 4004 Cov.: 32 AF XY: 0.210 AC XY: 15622 AN XY: 74362

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.210

Alfa AF: 0.173 Hom.: 4992

Bravo AF: 0.222

Asia WGS AF: 0.204 AC: 711 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.69

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: rs5762448; hg19: chr22-28408444;