chr1-231178475-A-G

Position:

• chr1-231178475-A-G

Variant summary

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

The NM_001004342.5(TRIM67):​c.1044+14462A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,136 control chromosomes in the GnomAD database, including 8,715 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 0.33 (8715 hom., cov: 33)
• Consequence: TRIM67 NM_001004342.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

Genes affected

TRIM67 (HGNC:31859): (tripartite motif containing 67) Predicted to enable zinc ion binding activity. Predicted to be involved in regulation of protein localization. Predicted to act upstream of or within negative regulation of Ras protein signal transduction; positive regulation of neuron projection development; and positive regulation of ubiquitin-dependent protein catabolic process. Predicted to be located in cytoplasm and cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM67	NM_001004342.5	c.1044+14462A>G		intron_variant		ENST00000366653.6
TRIM67	NM_001300889.3	c.858+14462A>G		intron_variant
TRIM67	NM_001410937.1	c.1044+14462A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM67	ENST00000366653.6	c.1044+14462A>G		intron_variant		1	NM_001004342.5	A1
TRIM67	ENST00000449018.7	c.858+14462A>G		intron_variant		1
TRIM67	ENST00000444294.7	c.1044+14462A>G		intron_variant		5		P3

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50546 AN: 152018 Hom.: 8691 Cov.: 33

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.333 AC: 50608 AN: 152136 Hom.: 8715 Cov.: 33 AF XY: 0.333 AC XY: 24799 AN XY: 74374

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.338

Alfa AF: 0.313 Hom.: 1321

Bravo AF: 0.340

Asia WGS AF: 0.399 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.36

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: rs9431663; hg19: chr1-231314221;