7-138472645-A-G

Position:

• chr7-138472645-A-G

Variant summary

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

The NM_015905.3(TRIM24):​c.364+11733A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,062 control chromosomes in the GnomAD database, including 52,473 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 0.83 (52473 hom., cov: 31)
• Consequence: TRIM24 NM_015905.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456

Genes affected

TRIM24 (HGNC:11812): (tripartite motif containing 24) The protein encoded by this gene mediates transcriptional control by interaction with the activation function 2 (AF2) region of several nuclear receptors, including the estrogen, retinoic acid, and vitamin D3 receptors. The protein localizes to nuclear bodies and is thought to associate with chromatin and heterochromatin-associated factors. The protein is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains - a RING, a B-box type 1 and a B-box type 2 - and a coiled-coil region. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

TRIM24 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM24	NM_015905.3	c.364+11733A>G		intron_variant		ENST00000343526.9	NP_056989.2
TRIM24	NM_003852.4	c.364+11733A>G		intron_variant			NP_003843.3
TRIM24	XM_024446981.2	c.307+11343A>G		intron_variant			XP_024302749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM24	ENST00000343526.9	c.364+11733A>G		intron_variant		1	NM_015905.3	ENSP00000340507.4
TRIM24	ENST00000415680.6	c.364+11733A>G		intron_variant		1		ENSP00000390829.2
TRIM24	ENST00000497516.5	n.238+11343A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125809 AN: 151944 Hom.: 52433 Cov.: 31

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.828 AC: 125907 AN: 152062 Hom.: 52473 Cov.: 31 AF XY: 0.822 AC XY: 61105 AN XY: 74344

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.817

Alfa AF: 0.834 Hom.: 82346

Bravo AF: 0.830

Asia WGS AF: 0.625 AC: 2176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.1
DANN	Benign	0.30

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: rs1874326; hg19: chr7-138157390;