rs3737825

Variant names:

• chr1-54721252-G-A
• rs3737825
• NM_004623.5:c.469+12G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-54721252-G-A
• chr1-54721252-G-T

Variant summary

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

The NM_004623.5(TTC4):​c.469+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 1,611,380 control chromosomes in the GnomAD database, including 5,202 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: 0.064 (4283 hom.)
• Consequence: TTC4 NM_004623.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC4	NM_004623.5	c.469+12G>A		intron_variant	Intron 4 of 9	ENST00000371281.4	NP_004614.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC4	ENST00000371281.4	c.469+12G>A		intron_variant	Intron 4 of 9	1	NM_004623.5	ENSP00000360329.3
MROH7-TTC4	ENST00000414150.6	n.*171+12G>A		intron_variant	Intron 27 of 32	2		ENSP00000410192.2

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14043 AN: 152052 Hom.: 914 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0808

GnomAD3 exomes AF: 0.0818 AC: 20523 AN: 250740 Hom.: 1207 AF XY: 0.0853 AC XY: 11561 AN XY: 135550

Gnomad AFR exome AF: 0.175

Gnomad AMR exome AF: 0.0377

Gnomad ASJ exome AF: 0.0431

Gnomad EAS exome AF: 0.145

Gnomad SAS exome AF: 0.180

Gnomad FIN exome AF: 0.0547

Gnomad NFE exome AF: 0.0549

Gnomad OTH exome AF: 0.0641

GnomAD4 exome AF: 0.0644 AC: 94007 AN: 1459210 Hom.: 4283 Cov.: 29 AF XY: 0.0680 AC XY: 49405 AN XY: 726082

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.0391

Gnomad4 ASJ exome AF: 0.0400

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.0530

Gnomad4 NFE exome AF: 0.0508

Gnomad4 OTH exome AF: 0.0738

GnomAD4 genome AF: 0.0924 AC: 14067 AN: 152170 Hom.: 919 Cov.: 32 AF XY: 0.0947 AC XY: 7047 AN XY: 74388

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.0507

Gnomad4 ASJ AF: 0.0403

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.0597

Gnomad4 NFE AF: 0.0520

Gnomad4 OTH AF: 0.0823

Alfa AF: 0.0691 Hom.: 117

Bravo AF: 0.0914

Asia WGS AF: 0.167 AC: 582 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.8
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3737825; hg19: chr1-55186925; COSMIC: COSV64884470; COSMIC: COSV64884470;