Genetic Variant ENSG00000285646:n.82C>G (chr1-11908021-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000661075.1(ENSG00000285646):n.82C>G 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 0.353 in 152,080 control chromosomes in the GnomAD database, including 9,873 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 0.35 ( 9873 hom., cov: 33)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

ENSG00000285646
ENST00000661075.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.523

Publications

8 publications found

Variant links:

Genes affected

ENSG00000285646 (HGNC:):

ENSG00000285646 links:

RNU5E-1 (HGNC:10215): (RNA, U5E small nuclear 1)

RNU5E-1 links:

Genome browser will be placed here

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=-0.48).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNU5E-1	NR_002754.3 link	n.-131C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000285646	ENST00000661075.1 link	n.82C>G	non_coding_transcript_exon_variant	Exon 1 of 2
RNU5E-1	ENST00000362477.2 link	n.-131C>G	upstream_gene_variant		6
ENSG00000285646	ENST00000649268.2 link	n.-126C>G	upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53563

AN:

151960

Hom.:

9857

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.459

Gnomad SAS

AF:

0.429

Gnomad FIN

AF:

0.496

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.346

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

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:

0.353

AC:

53618

AN:

152078

Hom.:

9873

Cov.:

AF XY:

0.360

AC XY:

26736

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.340

AC:

14092

AN:

41470

American (AMR)

AF:

0.336

AC:

5136

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

765

AN:

3470

East Asian (EAS)

AF:

0.460

AC:

2381

AN:

5176

South Asian (SAS)

AF:

0.428

AC:

2062

AN:

4822

European-Finnish (FIN)

AF:

0.496

AC:

5233

AN:

10558

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.338

AC:

22979

AN:

67982

Other (OTH)

AF:

0.347

AC:

732

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1783

3566

5348

7131

8914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.238

Hom.:

667

Bravo

AF:

0.337

Asia WGS

AF:

0.444

AC:

1543

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

3.2

(source)

DANN

Benign

0.50

PhyloP100

0.52

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