dbSNP rs9783068: ENSG00000293331:n.20+306A>G (chr1-630825-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000452176.2(ENSG00000293331):n.20+306A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000412 in 130,916 control chromosomes in the GnomAD database, including 8 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 0.00041 ( 8 hom., cov: 26)

Exomes 𝑓: 0.000059 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000293331
ENST00000452176.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.725

Publications

1 publications found

Variant links:

Genes affected

ENSG00000293331 (HGNC:):

ENSG00000293331 links:

LINC00115 (HGNC:26211): (long intergenic non-protein coding RNA 115)

LINC00115 links:

MTCO1P12 (HGNC:52014): (MT-CO1 pseudogene 12)

MTCO1P12 links:

MTND2P28 (HGNC:42129): (MT-ND2 pseudogene 28)

MTND2P28 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000452176.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BS2

High Homozygotes in GnomAd4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000452176.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ENSG00000293331	ENST00000452176.2	TSL:1	n.20+306A>G	intron	N/A
LINC00115	ENST00000419394.2	TSL:5	n.481-43870A>G	intron	N/A
ENSG00000293331	ENST00000440196.3	TSL:5	n.87-1819A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000413

AC:

AN:

130868

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000464

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000595

AC:

AN:

235428

Hom.:

AF XY:

0.0000920

AC XY:

AN XY:

119618

show subpopulations

African (AFR)

AF:

0.00146

AC:

AN:

5490

American (AMR)

AF:

0.00

AC:

AN:

7104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8754

East Asian (EAS)

AF:

0.00

AC:

AN:

20132

South Asian (SAS)

AF:

0.00

AC:

AN:

2338

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1152

European-Non Finnish (NFE)

AF:

0.0000329

AC:

AN:

152196

Other (OTH)

AF:

0.0000648

AC:

AN:

15438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.000412

AC:

AN:

130916

Hom.:

Cov.:

AF XY:

0.000487

AC XY:

AN XY:

63638

show subpopulations

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

African (AFR)

AF:

0.00148

AC:

AN:

28400

American (AMR)

AF:

0.000658

AC:

AN:

13678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3264

East Asian (EAS)

AF:

0.00

AC:

AN:

4642

South Asian (SAS)

AF:

0.00

AC:

AN:

3908

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9422

Middle Eastern (MID)

AF:

0.00

AC:

AN:

248

European-Non Finnish (NFE)

AF:

0.0000464

AC:

AN:

64694

Other (OTH)

AF:

0.00

AC:

AN:

1832

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000181302), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.354

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00523

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.2

(source)

DANN

Benign

0.70

PhyloP100

0.72

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over