rs1998027

Variant names:

• chr1-231190340-G-A
• rs1998027
• NM_001004342.5:c.1045-7031G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004342.5(TRIM67):​c.1045-7031G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,992 control chromosomes in the GnomAD database, including 29,181 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 0.59 (29181 hom., cov: 31)
• Consequence: TRIM67 NM_001004342.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004342.5. 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
	TRIM67	NM_001004342.5	MANE Select	c.1045-7031G>A		intron	N/A	NP_001004342.3
	TRIM67	NM_001410937.1		c.1045-7031G>A		intron	N/A	NP_001397866.1
	TRIM67	NM_001300889.3		c.859-7031G>A		intron	N/A	NP_001287818.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM67	ENST00000366653.6	TSL:1 MANE Select	c.1045-7031G>A		intron	N/A	ENSP00000355613.5
	TRIM67	ENST00000449018.7	TSL:1	c.859-7031G>A		intron	N/A	ENSP00000400163.3
	TRIM67	ENST00000444294.7	TSL:5	c.1045-7031G>A		intron	N/A	ENSP00000412124.3

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88858 AN: 151874 Hom.: 29114 Cov.: 31

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.585 AC: 88982 AN: 151992 Hom.: 29181 Cov.: 31 AF XY: 0.588 AC XY: 43704 AN XY: 74280

African (AFR) AF: 0.890 AC: 36920 AN: 41488

American (AMR) AF: 0.575 AC: 8783 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1804 AN: 3472

East Asian (EAS) AF: 0.701 AC: 3604 AN: 5144

South Asian (SAS) AF: 0.627 AC: 3015 AN: 4812

European-Finnish (FIN) AF: 0.424 AC: 4476 AN: 10566

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28647 AN: 67920

Other (OTH) AF: 0.564 AC: 1193 AN: 2114

Alfa AF: 0.465 Hom.: 47804

Bravo AF: 0.607

Asia WGS AF: 0.654 AC: 2278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.51
DANN	Benign	0.36
PhyloP100		-0.13
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: rs1998027; hg19: chr1-231326086;