rs11206424

chr1-54737871-G-A

Variant summary

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

The NM_004623.5(TTC4):c.1061+207G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 152,178 control chromosomes in the GnomAD database, including 446 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 0.067 (446 hom., cov: 32)
• Consequence: TTC4 NM_004623.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC4	NM_004623.5	c.1061+207G>A		intron_variant		ENST00000371281.4
MROH7-TTC4	NR_037639.2	n.5239+207G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC4	ENST00000371281.4	c.1061+207G>A		intron_variant		1	NM_004623.5	P1
TTC4	ENST00000371284.9	n.1227+207G>A		intron_variant, non_coding_transcript_variant		5
TTC4	ENST00000486091.1	n.976+207G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10176 AN: 152060 Hom.: 445 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0393

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.0593

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0474

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0669 AC: 10180 AN: 152178 Hom.: 446 Cov.: 32 AF XY: 0.0665 AC XY: 4945 AN XY: 74402

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0392

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0758

Gnomad4 FIN AF: 0.0593

Gnomad4 NFE AF: 0.0475

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0623 Hom.: 46

Bravo AF: 0.0657

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.49
Dann	Benign	0.57

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: rs11206424; hg19: chr1-55203544;