15-64388192-C-A

Position:

• chr15-64388192-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016213.5(TRIP4):​c.101+228C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 672,588 control chromosomes in the GnomAD database, including 609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (455 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (154 hom.)
• Consequence: TRIP4 NM_016213.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0630

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 15-64388192-C-A is Benign according to our data. Variant chr15-64388192-C-A is described in ClinVar as [Benign]. Clinvar id is 1251827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIP4	NM_016213.5	c.101+228C>A		intron_variant		ENST00000261884.8	NP_057297.2
TRIP4	NM_001321924.2	c.-590+144C>A		intron_variant			NP_001308853.1
TRIP4	NR_135855.2	n.129+228C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIP4	ENST00000261884.8	c.101+228C>A		intron_variant		1	NM_016213.5	ENSP00000261884	P1

Frequencies

GnomAD3 genomes AF: 0.0423 AC: 6440 AN: 152082 Hom.: 451 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.00467 AC: 2428 AN: 520388 Hom.: 154 AF XY: 0.00418 AC XY: 1079 AN XY: 258006

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.0155

Gnomad4 ASJ exome AF: 0.00646

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000328

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000550

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.0425 AC: 6466 AN: 152200 Hom.: 455 Cov.: 32 AF XY: 0.0396 AC XY: 2944 AN XY: 74420

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000823

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0424 Hom.: 56

Bravo AF: 0.0492

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.50

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: rs16947927; hg19: chr15-64680391;