dbSNP rs41534051: NSUN4:n.*1760T>C (chr1-46363062-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000307089.7(NSUN4):n.*1760T>C 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 0.224 in 151,926 control chromosomes in the GnomAD database, including 4,275 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 ( 4274 hom., cov: 31)

Exomes 𝑓: 0.67 ( 1 hom. )

Consequence

NSUN4
ENST00000307089.7 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0430

Publications

11 publications found

Variant links:

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]

NSUN4 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSUN4	NM_199044.4 link	c.*1216T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000474844.6	NP_950245.2	Q96CB9-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NSUN4	ENST00000307089.7 link	n.*1760T>C	non_coding_transcript_exon_variant	Exon 5 of 5	1		ENSP00000471937.1	M0R1K5
NSUN4	ENST00000474844.6 link	c.*1216T>C	3_prime_UTR_variant	Exon 6 of 6	1	NM_199044.4	ENSP00000419740.1	Q96CB9-1
NSUN4	ENST00000307089.7 link	n.*1760T>C	3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000471937.1	M0R1K5
NSUN4	ENST00000718455.1 link	c.606+1366T>C	intron_variant	Intron 6 of 6			ENSP00000520833.1

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

33982

AN:

151802

Hom.:

4274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.0204

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.252

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.221

GnomAD4 exome

AF:

0.667

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.224

AC:

33977

AN:

151920

Hom.:

4274

Cov.:

AF XY:

0.219

AC XY:

16257

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.148

AC:

6132

AN:

41448

American (AMR)

AF:

0.186

AC:

2834

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

651

AN:

3460

East Asian (EAS)

AF:

0.0206

AC:

107

AN:

5188

South Asian (SAS)

AF:

0.108

AC:

519

AN:

4818

European-Finnish (FIN)

AF:

0.309

AC:

3245

AN:

10500

Middle Eastern (MID)

AF:

0.250

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.291

AC:

19750

AN:

67948

Other (OTH)

AF:

0.217

AC:

456

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1245

2489

3734

4978

6223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.250

Hom.:

1323

Bravo

AF:

0.215

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

-0.96

CADD

Benign

2.8

(source)

DANN

Benign

0.67

PhyloP100

-0.043

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over