1-46341031-A-G

Position:

• chr1-46341031-A-G

Variant summary

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

The NM_199044.4(NSUN4):​c.93+112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,168,154 control chromosomes in the GnomAD database, including 42,190 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 0.23 (4412 hom., cov: 31)
  • Exomes 𝑓: 0.26 (37778 hom.)
• Consequence: NSUN4 NM_199044.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSUN4	NM_199044.4	c.93+112A>G		intron_variant		ENST00000474844.6	NP_950245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSUN4	ENST00000474844.6	c.93+112A>G		intron_variant		1	NM_199044.4	ENSP00000419740	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34587 AN: 151898 Hom.: 4412 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.261 AC: 264908 AN: 1016138 Hom.: 37778 Cov.: 13 AF XY: 0.256 AC XY: 129699 AN XY: 505762

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.0109

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.302

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.227 AC: 34582 AN: 152016 Hom.: 4412 Cov.: 31 AF XY: 0.223 AC XY: 16562 AN XY: 74282

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.0174

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.221

Alfa AF: 0.265 Hom.: 2646

Bravo AF: 0.219

Asia WGS AF: 0.0760 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.4
DANN	Benign	0.58

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: rs10489769; hg19: chr1-46806703;