rs7948996

Positions:

• chr11-5710992-G-T

Variant summary

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

The ENST00000412903.1(TRIM5):​c.-61-30754C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,214 control chromosomes in the GnomAD database, including 8,773 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 0.32 (8773 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM5 ENST00000412903.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

Genes affected

TRIM5 (HGNC:16276): (tripartite motif containing 5) The protein encoded by this gene 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. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

TRIM22 (HGNC:16379): (tripartite motif containing 22) The protein encoded by this gene 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. This protein localizes to the cytoplasm and its expression is induced by interferon. The protein is involved in innate immunity against different DNA and RNA viruses. [provided by RefSeq, Oct 2021]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM5	ENST00000412903.1	c.-61-30754C>A		intron_variant		1		ENSP00000388031
TRIM5	ENST00000380027.5	c.-440-25598C>A		intron_variant		5		ENSP00000369366
TRIM22	ENST00000429063.5	c.93+2389G>T		intron_variant		2		ENSP00000409991

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47765 AN: 151108 Hom.: 8749 Cov.: 31

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.314

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.316 AC: 47848 AN: 151214 Hom.: 8773 Cov.: 31 AF XY: 0.315 AC XY: 23225 AN XY: 73792

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.314

Alfa AF: 0.269 Hom.: 767

Bravo AF: 0.339

Asia WGS AF: 0.319 AC: 1109 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7948996; hg19: chr11-5732222;