chr1-54717459-A-G

Position:

• chr1-54717459-A-G

Variant summary

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

The NM_004623.5(TTC4):​c.230-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 1,462,854 control chromosomes in the GnomAD database, including 4,427 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 0.092 (919 hom., cov: 32)
  • Exomes 𝑓: 0.062 (3508 hom.)
• Consequence: TTC4 NM_004623.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424

Genes affected

TTC4 (HGNC:12394): (tetratricopeptide repeat domain 4) This gene encodes a protein that contains tetratricopeptide (TPR) repeats, which often mediate protein-protein interactions and chaperone activity. The encoded protein interacts with heat shock proteins 70 and 90. Alternative splicing results in multiple transcript variants. Naturally-occuring readthrough transcription occurs from upstream gene MROH (maestro heat-like repeat family member 7) to this gene. [provided by RefSeq, Apr 2014]

MROH7-TTC4 (HGNC:49180): (MROH7-TTC4 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MROH7 (maestro heat-like repeat family member 7) and TTC4 (tetratricopeptide repeat domain 4) genes. Alternative splicing results in multiple transcript variants, which are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to produce protein products. [provided by RefSeq, Aug 2013]

TTC4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC4	NM_004623.5	c.230-33A>G		intron_variant		ENST00000371281.4	NP_004614.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC4	ENST00000371281.4	c.230-33A>G		intron_variant		1	NM_004623.5	ENSP00000360329.3
MROH7-TTC4	ENST00000414150.6	n.3937-33A>G		intron_variant		2		ENSP00000410192.2

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 14018 AN: 152138 Hom.: 915 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0593

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0808

GnomAD3 exomes AF: 0.0791 AC: 12874 AN: 162714 Hom.: 722 AF XY: 0.0803 AC XY: 7071 AN XY: 88026

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.0361

Gnomad ASJ exome AF: 0.0414

Gnomad EAS exome AF: 0.143

Gnomad SAS exome AF: 0.185

Gnomad FIN exome AF: 0.0541

Gnomad NFE exome AF: 0.0544

Gnomad OTH exome AF: 0.0683

GnomAD4 exome AF: 0.0625 AC: 81909 AN: 1310598 Hom.: 3508 Cov.: 29 AF XY: 0.0650 AC XY: 41764 AN XY: 642196

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.0395

Gnomad4 ASJ exome AF: 0.0399

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.0533

Gnomad4 NFE exome AF: 0.0509

Gnomad4 OTH exome AF: 0.0739

GnomAD4 genome AF: 0.0922 AC: 14040 AN: 152256 Hom.: 919 Cov.: 32 AF XY: 0.0946 AC XY: 7043 AN XY: 74462

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0505

Gnomad4 ASJ AF: 0.0403

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.0593

Gnomad4 NFE AF: 0.0520

Gnomad4 OTH AF: 0.0818

Alfa AF: 0.0602 Hom.: 719

Bravo AF: 0.0912

Asia WGS AF: 0.167 AC: 581 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.2
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3766415; hg19: chr1-55183132; COSMIC: COSV64884466;