chr7-99891948-G-A

Variant names:

• chr7-99891948-G-A
• rs17277546
• NM_033091.3:c.*215C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_033091.3(TRIM4):​c.*215C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 485,818 control chromosomes in the GnomAD database, including 395 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 0.031 (109 hom., cov: 32)
  • Exomes 𝑓: 0.037 (286 hom.)
• Consequence: TRIM4 NM_033091.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 30 publications found

Genes affected

TRIM4 (HGNC:16275): (tripartite motif containing 4) 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 localizes to cytoplasmic bodies. Its function has not been identified. Alternatively spliced transcript variants that encode different isoforms have been described.[provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0312 (4749/152258) while in subpopulation NFE AF = 0.0455 (3093/68008). AF 95% confidence interval is 0.0441. There are 109 homozygotes in GnomAd4. There are 2300 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 109 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033091.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM4	NM_033091.3	MANE Select	c.*215C>T		3_prime_UTR	Exon 6 of 6	NP_149082.1	Q9C037-2
	TRIM4	NM_033017.4		c.*215C>T		3_prime_UTR	Exon 7 of 7	NP_148977.2	Q9C037-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM4	ENST00000349062.7	TSL:1 MANE Select	c.*215C>T		3_prime_UTR	Exon 6 of 6	ENSP00000275736.4	Q9C037-2
	TRIM4	ENST00000355947.6	TSL:1	c.*215C>T		3_prime_UTR	Exon 7 of 7	ENSP00000348216.2	Q9C037-1
	TRIM4	ENST00000953520.1		c.*215C>T		3_prime_UTR	Exon 6 of 6	ENSP00000623579.1

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4750 AN: 152140 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.00828

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0291

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0455

Gnomad OTH AF: 0.0320

GnomAD4 exome AF: 0.0371 AC: 12372 AN: 333560 Hom.: 286 Cov.: 4 AF XY: 0.0372 AC XY: 6365 AN XY: 170896

African (AFR) AF: 0.00922 AC: 97 AN: 10518

American (AMR) AF: 0.0235 AC: 262 AN: 11142

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 203 AN: 11174

East Asian (EAS) AF: 0.0000746 AC: 2 AN: 26808

South Asian (SAS) AF: 0.0181 AC: 304 AN: 16800

European-Finnish (FIN) AF: 0.0584 AC: 1430 AN: 24472

Middle Eastern (MID) AF: 0.0245 AC: 38 AN: 1554

European-Non Finnish (NFE) AF: 0.0446 AC: 9393 AN: 210566

Other (OTH) AF: 0.0313 AC: 643 AN: 20526

GnomAD4 genome AF: 0.0312 AC: 4749 AN: 152258 Hom.: 109 Cov.: 32 AF XY: 0.0309 AC XY: 2300 AN XY: 74448

African (AFR) AF: 0.00825 AC: 343 AN: 41564

American (AMR) AF: 0.0289 AC: 442 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0176 AC: 85 AN: 4824

European-Finnish (FIN) AF: 0.0596 AC: 632 AN: 10598

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0455 AC: 3093 AN: 68008

Other (OTH) AF: 0.0317 AC: 67 AN: 2114

Alfa AF: 0.0406 Hom.: 642

Bravo AF: 0.0279

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.0
DANN	Benign	0.76
PhyloP100		0.20
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: rs17277546; hg19: chr7-99489571;