rs12073998

Variant names:

• chr1-46377860-T-C
• rs12073998
• NM_001387270.1:c.879-5976T>C

Variant summary

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

The NM_001387270.1(NSUN4):​c.879-5976T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,912 control chromosomes in the GnomAD database, including 13,879 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 0.42 (13879 hom., cov: 31)
• Consequence: NSUN4 NM_001387270.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 7 publications found

Genes affected

NSUN4 (HGNC:31802): (NOP2/Sun RNA methyltransferase 4) Enables rRNA (cytosine-C5-)-methyltransferase activity. Involved in rRNA methylation. Part of mitochondrial large ribosomal subunit. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387270.1. 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
	NSUN4	NM_001387270.1		c.879-5976T>C		intron	N/A	NP_001374199.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64345 AN: 151794 Hom.: 13843 Cov.: 31

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.424 AC: 64416 AN: 151912 Hom.: 13879 Cov.: 31 AF XY: 0.422 AC XY: 31329 AN XY: 74242

African (AFR) AF: 0.479 AC: 19817 AN: 41406

American (AMR) AF: 0.330 AC: 5033 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1251 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1694 AN: 5172

South Asian (SAS) AF: 0.510 AC: 2456 AN: 4818

European-Finnish (FIN) AF: 0.401 AC: 4222 AN: 10518

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.421 AC: 28598 AN: 67946

Other (OTH) AF: 0.426 AC: 901 AN: 2114

Alfa AF: 0.417 Hom.: 2071

Bravo AF: 0.418

Asia WGS AF: 0.400 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.75
DANN	Benign	0.50
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs12073998; hg19: chr1-46843532;