7-138472645-A-G

Variant names:

• chr7-138472645-A-G
• rs1874326
• NM_015905.3:c.364+11733A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015905.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM24	NM_015905.3	MANE Select	c.364+11733A>G		intron	N/A	NP_056989.2
	TRIM24	NM_003852.4		c.364+11733A>G		intron	N/A	NP_003843.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM24	ENST00000343526.9	TSL:1 MANE Select	c.364+11733A>G		intron	N/A	ENSP00000340507.4
	TRIM24	ENST00000415680.6	TSL:1	c.364+11733A>G		intron	N/A	ENSP00000390829.2
	TRIM24	ENST00000497516.5	TSL:5	n.238+11343A>G		intron	N/A

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

African (AFR) AF: 0.845 AC: 35047 AN: 41466

American (AMR) AF: 0.830 AC: 12678 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3011 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2689 AN: 5136

South Asian (SAS) AF: 0.715 AC: 3443 AN: 4818

European-Finnish (FIN) AF: 0.774 AC: 8192 AN: 10588

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58104 AN: 67996

Other (OTH) AF: 0.817 AC: 1729 AN: 2116

Alfa AF: 0.834 Hom.: 186819

Bravo AF: 0.830

Asia WGS AF: 0.625 AC: 2176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.1
DANN	Benign	0.30
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1874326; hg19: chr7-138157390;