rs1180937

Positions:

• chr1-54725971-T-C

Variant summary

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

The NM_004623.5(TTC4):​c.595-2375T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,056 control chromosomes in the GnomAD database, including 49,623 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 0.80 (49623 hom., cov: 31)
• Consequence: TTC4 NM_004623.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC4	NM_004623.5	c.595-2375T>C		intron_variant		ENST00000371281.4
MROH7-TTC4	NR_037639.2	n.4773-2375T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC4	ENST00000371281.4	c.595-2375T>C		intron_variant		1	NM_004623.5	P1
TTC4	ENST00000371284.9	n.761-2375T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122221 AN: 151938 Hom.: 49605 Cov.: 31

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.815

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

GnomAD4 genome AF: 0.804 AC: 122285 AN: 152056 Hom.: 49623 Cov.: 31 AF XY: 0.811 AC XY: 60268 AN XY: 74342

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.853

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.876

Gnomad4 FIN AF: 0.911

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.817

Alfa AF: 0.836 Hom.: 77425

Bravo AF: 0.792

Asia WGS AF: 0.891 AC: 3097 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	0.21
DANN	Benign	0.92

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: rs1180937; hg19: chr1-55191644; COSMIC: COSV64884487;