15-64388193-A-G

Position:

• chr15-64388193-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016213.5(TRIP4):​c.101+229A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 656,762 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (33 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (13 hom.)
• Consequence: TRIP4 NM_016213.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.355

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 15-64388193-A-G is Benign according to our data. Variant chr15-64388193-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1215423.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1979/152262) while in subpopulation AFR AF= 0.046 (1912/41536). AF 95% confidence interval is 0.0443. There are 33 homozygotes in gnomad4. There are 927 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIP4	NM_016213.5	c.101+229A>G		intron_variant		ENST00000261884.8	NP_057297.2
TRIP4	NM_001321924.2	c.-590+145A>G		intron_variant			NP_001308853.1
TRIP4	NR_135855.2	n.129+229A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIP4	ENST00000261884.8	c.101+229A>G		intron_variant		1	NM_016213.5	ENSP00000261884	P1

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1980 AN: 152144 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.00135 AC: 679 AN: 504500 Hom.: 13 AF XY: 0.00123 AC XY: 307 AN XY: 250590

Gnomad4 AFR exome AF: 0.0406

Gnomad4 AMR exome AF: 0.00348

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000551

Gnomad4 FIN exome AF: 0.0000517

Gnomad4 NFE exome AF: 0.000158

Gnomad4 OTH exome AF: 0.00330

GnomAD4 genome AF: 0.0130 AC: 1979 AN: 152262 Hom.: 33 Cov.: 32 AF XY: 0.0125 AC XY: 927 AN XY: 74436

Gnomad4 AFR AF: 0.0460

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00999 Hom.: 2

Bravo AF: 0.0146

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.45

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: rs141300147; hg19: chr15-64680392;