chr4-8504613-T-G

Variant names:

• chr4-8504613-T-G
• rs2631723
• XM_047449679.1:c.2045-4185T>G

Variant summary

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

The ENST00000528132.1(ENSG00000205959):​n.171-4185T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,064 control chromosomes in the GnomAD database, including 34,924 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 0.67 (34924 hom., cov: 32)
• Consequence: ENSG00000205959 ENST00000528132.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• Publications: 5 publications found

Genes affected

TRMT44 (HGNC:26653): (tRNA methyltransferase 44 homolog) The protein encoded by this gene is a putative tRNA methyltransferase found in the cytoplasm. Defects in this gene may be a cause of partial epilepsy with pericentral spikes (PEPS), but that has not been proven definitively. [provided by RefSeq, May 2012]

ENSG00000205959 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000528132.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000205959	ENST00000528132.1	TSL:4	n.171-4185T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101111 AN: 151946 Hom.: 34872 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.666 AC: 101228 AN: 152064 Hom.: 34924 Cov.: 32 AF XY: 0.665 AC XY: 49424 AN XY: 74332

African (AFR) AF: 0.866 AC: 35928 AN: 41494

American (AMR) AF: 0.662 AC: 10111 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2005 AN: 3470

East Asian (EAS) AF: 0.590 AC: 3033 AN: 5138

South Asian (SAS) AF: 0.524 AC: 2528 AN: 4826

European-Finnish (FIN) AF: 0.607 AC: 6427 AN: 10596

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39157 AN: 67946

Other (OTH) AF: 0.650 AC: 1369 AN: 2106

Alfa AF: 0.597 Hom.: 14274

Bravo AF: 0.683

Asia WGS AF: 0.599 AC: 2082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.53
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs2631723; hg19: chr4-8506340;