rs74615166

Positions:

• chr15-64433291-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_016213.5(TRIP4):​c.1575+7660T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 152,250 control chromosomes in the GnomAD database, including 25 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 0.016 (25 hom., cov: 32)
• Consequence: TRIP4 NM_016213.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328

Genes affected

TRIP4 (HGNC:12310): (thyroid hormone receptor interactor 4) This gene encodes a subunit of the tetrameric nuclear activating signal cointegrator 1 (ASC-1) complex, which associates with transcriptional coactivators, nuclear receptors and basal transcription factors to facilitate nuclear receptors-mediated transcription. This protein is localized in the nucleus and contains an E1A-type zinc finger domain, which mediates interaction with transcriptional coactivators and ligand-bound nuclear receptors, such as thyroid hormone receptor and retinoid X receptor alpha, but not glucocorticoid receptor. Mutations in this gene are associated with spinal muscular atrophy with congenital bone fractures-1 (SMABF1). [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0157 (2397/152250) while in subpopulation SAS AF= 0.0247 (119/4820). AF 95% confidence interval is 0.0211. There are 25 homozygotes in gnomad4. There are 1208 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIP4	NM_016213.5	c.1575+7660T>C		intron_variant		ENST00000261884.8	NP_057297.2
TRIP4	NM_001321924.2	c.885+7660T>C		intron_variant			NP_001308853.1
TRIP4	NR_135855.2	n.1476+7660T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIP4	ENST00000261884.8	c.1575+7660T>C		intron_variant		1	NM_016213.5	ENSP00000261884	P1
TRIP4	ENST00000558162.1	c.133+7660T>C		intron_variant		3		ENSP00000452764
TRIP4	ENST00000560475.1	c.112-11715T>C		intron_variant		3		ENSP00000454558

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2403 AN: 152132 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.00393

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0249

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0218

Gnomad OTH AF: 0.0225

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

GnomAD4 genome AF: 0.0157 AC: 2397 AN: 152250 Hom.: 25 Cov.: 32 AF XY: 0.0162 AC XY: 1208 AN XY: 74442

Gnomad4 AFR AF: 0.00392

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0247

Gnomad4 FIN AF: 0.0302

Gnomad4 NFE AF: 0.0218

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0195 Hom.: 7

Bravo AF: 0.0140

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.77
DANN	Benign	0.61

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: rs74615166; hg19: chr15-64725490;