rs4140571

Variant names:

• chr22-28027390-C-A
• rs4140571
• NM_001145418.2:c.4073+2836G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-28027390-C-A
• chr22-28027390-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145418.2(TTC28):​c.4073+2836G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,146 control chromosomes in the GnomAD database, including 28,104 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 0.59 (28104 hom., cov: 33)
• Consequence: TTC28 NM_001145418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC28	NM_001145418.2	c.4073+2836G>T		intron_variant	Intron 13 of 22	ENST00000397906.7	NP_001138890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC28	ENST00000397906.7	c.4073+2836G>T		intron_variant	Intron 13 of 22	1	NM_001145418.2	ENSP00000381003.2
TTC28	ENST00000612946.4	c.3692+2836G>T		intron_variant	Intron 11 of 20	5		ENSP00000479834.1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90211 AN: 152028 Hom.: 28044 Cov.: 33

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.594 AC: 90329 AN: 152146 Hom.: 28104 Cov.: 33 AF XY: 0.598 AC XY: 44442 AN XY: 74372

African (AFR) AF: 0.781 AC: 32447 AN: 41534

American (AMR) AF: 0.561 AC: 8574 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2201 AN: 3468

East Asian (EAS) AF: 0.640 AC: 3309 AN: 5170

South Asian (SAS) AF: 0.695 AC: 3353 AN: 4826

European-Finnish (FIN) AF: 0.502 AC: 5310 AN: 10578

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33373 AN: 67966

Other (OTH) AF: 0.580 AC: 1224 AN: 2112

Alfa AF: 0.561 Hom.: 4316

Bravo AF: 0.598

Asia WGS AF: 0.669 AC: 2325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.80
PhyloP100		0.077
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4140571; hg19: chr22-28423378;