1-46340808-C-T

Variant names:

• chr1-46340808-C-T
• rs17361749
• ENST00000307089.7:n.-19C>T

Variant summary

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

The ENST00000307089.7(NSUN4):​n.-19C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,599,658 control chromosomes in the GnomAD database, including 59,791 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 0.22 (4266 hom., cov: 31)
  • Exomes 𝑓: 0.27 (55525 hom.)
• Consequence: NSUN4 ENST00000307089.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 31 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=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000307089.7. 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_199044.4	MANE Select	c.-19C>T		5_prime_UTR	Exon 1 of 6	NP_950245.2
	NSUN4	NR_045789.2		n.2C>T		non_coding_transcript_exon	Exon 1 of 7
	NSUN4	NR_045790.2		n.2C>T		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSUN4	ENST00000307089.7	TSL:1	n.-19C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000471937.1
	NSUN4	ENST00000474844.6	TSL:1 MANE Select	c.-19C>T		5_prime_UTR	Exon 1 of 6	ENSP00000419740.1
	NSUN4	ENST00000307089.7	TSL:1	n.-19C>T		5_prime_UTR	Exon 1 of 5	ENSP00000471937.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33625 AN: 152072 Hom.: 4267 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.222

GnomAD2 exomes AF: 0.210 AC: 47867 AN: 228318 AF XY: 0.211

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.127

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.0211

Gnomad FIN exome AF: 0.302

Gnomad NFE exome AF: 0.292

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.267 AC: 385965 AN: 1447468 Hom.: 55525 Cov.: 30 AF XY: 0.262 AC XY: 188722 AN XY: 719444

African (AFR) AF: 0.126 AC: 4164 AN: 33066

American (AMR) AF: 0.135 AC: 5762 AN: 42714

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 4980 AN: 25632

East Asian (EAS) AF: 0.0162 AC: 631 AN: 39044

South Asian (SAS) AF: 0.109 AC: 9215 AN: 84612

European-Finnish (FIN) AF: 0.302 AC: 15832 AN: 52430

Middle Eastern (MID) AF: 0.188 AC: 1060 AN: 5650

European-Non Finnish (NFE) AF: 0.299 AC: 330320 AN: 1104598

Other (OTH) AF: 0.234 AC: 14001 AN: 59722

GnomAD4 genome AF: 0.221 AC: 33619 AN: 152190 Hom.: 4266 Cov.: 31 AF XY: 0.216 AC XY: 16102 AN XY: 74398

African (AFR) AF: 0.134 AC: 5545 AN: 41520

American (AMR) AF: 0.185 AC: 2832 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3472

East Asian (EAS) AF: 0.0214 AC: 111 AN: 5182

South Asian (SAS) AF: 0.103 AC: 498 AN: 4828

European-Finnish (FIN) AF: 0.311 AC: 3287 AN: 10574

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19944 AN: 67998

Other (OTH) AF: 0.218 AC: 460 AN: 2114

Alfa AF: 0.271 Hom.: 6488

Bravo AF: 0.212

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		0.18
PromoterAI		0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=299/1	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: rs17361749; hg19: chr1-46806480; COSMIC: COSV107396642; COSMIC: COSV107396642;