chr1-54730426-G-A

Variant names:

• chr1-54730426-G-A
• rs4926653
• NM_004623.5:c.682-1060G>A

Variant summary

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

The NM_004623.5(TTC4):​c.682-1060G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,904 control chromosomes in the GnomAD database, including 25,739 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 0.57 (25739 hom., cov: 31)
• Consequence: TTC4 NM_004623.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927
• Publications: 1 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004623.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC4	NM_004623.5	MANE Select	c.682-1060G>A		intron	N/A	NP_004614.3
	TTC4	NM_001291333.2		c.681+1994G>A		intron	N/A	NP_001278262.1
	MROH7-TTC4	NR_037639.2		n.4860-1060G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC4	ENST00000371281.4	TSL:1 MANE Select	c.682-1060G>A		intron	N/A	ENSP00000360329.3
	MROH7-TTC4	ENST00000414150.6	TSL:2	n.*384-1060G>A		intron	N/A	ENSP00000410192.2
	TTC4	ENST00000371284.9	TSL:5	n.848-1060G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86897 AN: 151784 Hom.: 25718 Cov.: 31

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.573 AC: 86970 AN: 151904 Hom.: 25739 Cov.: 31 AF XY: 0.577 AC XY: 42855 AN XY: 74220

African (AFR) AF: 0.610 AC: 25257 AN: 41392

American (AMR) AF: 0.578 AC: 8825 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2003 AN: 3472

East Asian (EAS) AF: 0.966 AC: 5005 AN: 5182

South Asian (SAS) AF: 0.727 AC: 3493 AN: 4806

European-Finnish (FIN) AF: 0.533 AC: 5625 AN: 10544

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34848 AN: 67936

Other (OTH) AF: 0.554 AC: 1168 AN: 2110

Alfa AF: 0.540 Hom.: 85903

Bravo AF: 0.580

Asia WGS AF: 0.807 AC: 2806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.8
DANN	Benign	0.74
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4926653; hg19: chr1-55196099;