8-144079996-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_019037.3(EXOSC4):​c.225A>G​(p.Gln75Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00661 in 1,614,074 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0068 ( 43 hom. )

Consequence

EXOSC4
NM_019037.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.07
Variant links:
Genes affected
EXOSC4 (HGNC:18189): (exosome component 4) Enables mRNA 3'-UTR AU-rich region binding activity. Involved in nucleic acid metabolic process and positive regulation of cell growth. Acts upstream of or within defense response to virus. Located in cytosol; nucleoplasm; and transcriptionally active chromatin. Part of exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]
MIR6847 (HGNC:50022): (microRNA 6847) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 8-144079996-A-G is Benign according to our data. Variant chr8-144079996-A-G is described in ClinVar as [Benign]. Clinvar id is 774253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=3.07 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 43 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EXOSC4NM_019037.3 linkc.225A>G p.Gln75Gln synonymous_variant Exon 2 of 3 ENST00000316052.6 NP_061910.1 Q9NPD3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EXOSC4ENST00000316052.6 linkc.225A>G p.Gln75Gln synonymous_variant Exon 2 of 3 1 NM_019037.3 ENSP00000315476.4 Q9NPD3
ENSG00000290230ENST00000703646.1 linkn.225A>G non_coding_transcript_exon_variant Exon 2 of 8 ENSP00000515414.1 A0A994J4D9

Frequencies

GnomAD3 genomes
AF:
0.00450
AC:
685
AN:
152214
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00150
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00242
Gnomad ASJ
AF:
0.000865
Gnomad EAS
AF:
0.00173
Gnomad SAS
AF:
0.00456
Gnomad FIN
AF:
0.00273
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00751
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00492
AC:
1236
AN:
251336
Hom.:
5
AF XY:
0.00502
AC XY:
682
AN XY:
135866
show subpopulations
Gnomad AFR exome
AF:
0.00111
Gnomad AMR exome
AF:
0.00214
Gnomad ASJ exome
AF:
0.000496
Gnomad EAS exome
AF:
0.00266
Gnomad SAS exome
AF:
0.00340
Gnomad FIN exome
AF:
0.00259
Gnomad NFE exome
AF:
0.00792
Gnomad OTH exome
AF:
0.00489
GnomAD4 exome
AF:
0.00682
AC:
9976
AN:
1461742
Hom.:
43
Cov.:
31
AF XY:
0.00668
AC XY:
4859
AN XY:
727146
show subpopulations
Gnomad4 AFR exome
AF:
0.000986
Gnomad4 AMR exome
AF:
0.00197
Gnomad4 ASJ exome
AF:
0.000842
Gnomad4 EAS exome
AF:
0.00161
Gnomad4 SAS exome
AF:
0.00335
Gnomad4 FIN exome
AF:
0.00360
Gnomad4 NFE exome
AF:
0.00800
Gnomad4 OTH exome
AF:
0.00555
GnomAD4 genome
AF:
0.00451
AC:
687
AN:
152332
Hom.:
1
Cov.:
33
AF XY:
0.00422
AC XY:
314
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.00152
Gnomad4 AMR
AF:
0.00242
Gnomad4 ASJ
AF:
0.000865
Gnomad4 EAS
AF:
0.00173
Gnomad4 SAS
AF:
0.00477
Gnomad4 FIN
AF:
0.00273
Gnomad4 NFE
AF:
0.00751
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00575
Hom.:
1
Bravo
AF:
0.00422
Asia WGS
AF:
0.00346
AC:
12
AN:
3478
EpiCase
AF:
0.00774
EpiControl
AF:
0.00693

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jun 06, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
6.3
DANN
Benign
0.68

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs111633196; hg19: chr8-145134899; COSMIC: COSV60156727; COSMIC: COSV60156727; API