rs7629889

Variant names:

• chr3-3145959-G-A
• rs7629889
• NM_182916.3:c.609-471G>A

Variant summary

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

The NM_182916.3(TRNT1):​c.609-471G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,250 control chromosomes in the GnomAD database, including 1,569 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 0.14 (1569 hom., cov: 30)
• Consequence: TRNT1 NM_182916.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 7 publications found

Genes affected

TRNT1 (HGNC:17341): (tRNA nucleotidyl transferase 1) The protein encoded by this gene is a CCA-adding enzyme which belongs to the tRNA nucleotidyltransferase/poly(A) polymerase family. This essential enzyme functions by catalyzing the addition of the conserved nucleotide triplet CCA to the 3' terminus of tRNA molecules. Mutations in this gene result in sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

CRBN (HGNC:30185): (cereblon) This gene encodes a protein related to the Lon protease protein family. In rodents and other mammals this gene product is found in the cytoplasm localized with a calcium channel membrane protein, and is thought to play a role in brain development. Mutations in this gene are associated with autosomal recessive nonsyndromic cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

CRBN Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal recessive 2

  Inheritance: AR Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182916.3. 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
	TRNT1	NM_182916.3	MANE Select	c.609-471G>A		intron	N/A	NP_886552.3	Q96Q11-1
	TRNT1	NM_001367321.1		c.609-471G>A		intron	N/A	NP_001354250.1	Q96Q11-1
	TRNT1	NM_001367322.1		c.609-471G>A		intron	N/A	NP_001354251.1	Q96Q11-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRNT1	ENST00000251607.11	TSL:1 MANE Select	c.609-471G>A		intron	N/A	ENSP00000251607.6	Q96Q11-1
	TRNT1	ENST00000280591.10	TSL:1	c.609-471G>A		intron	N/A	ENSP00000280591.6	Q96Q11-2
	CRBN	ENST00000639284.1	TSL:5	c.1312-460C>T		intron	N/A	ENSP00000491442.1	A0A1W2PPJ5

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21369 AN: 151132 Hom.: 1564 Cov.: 30

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0571

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.142 AC: 21402 AN: 151250 Hom.: 1569 Cov.: 30 AF XY: 0.142 AC XY: 10483 AN XY: 73812

African (AFR) AF: 0.150 AC: 6158 AN: 41176

American (AMR) AF: 0.170 AC: 2554 AN: 15054

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 428 AN: 3464

East Asian (EAS) AF: 0.0572 AC: 296 AN: 5174

South Asian (SAS) AF: 0.155 AC: 744 AN: 4786

European-Finnish (FIN) AF: 0.142 AC: 1481 AN: 10410

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9339 AN: 67904

Other (OTH) AF: 0.135 AC: 280 AN: 2080

Alfa AF: 0.145 Hom.: 1150

Bravo AF: 0.148

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.72
DANN	Benign	0.85
PhyloP100		-1.1
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: rs7629889; hg19: chr3-3187643;