Menu
GeneBe

1-183545018-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001375584.1(SMG7):c.2076A>G(p.Pro692=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,613,818 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 11 hom., cov: 32)
Exomes 𝑓: 0.0036 ( 55 hom. )

Consequence

SMG7
NM_001375584.1 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.230
Variant links:
Genes affected
SMG7 (HGNC:16792): (SMG7 nonsense mediated mRNA decay factor) This gene encodes a protein that is essential for nonsense-mediated mRNA decay (NMD); a process whereby transcripts with premature termination codons are targeted for rapid degradation by a mRNA decay complex. The mRNA decay complex consists, in part, of this protein along with proteins SMG5 and UPF1. The N-terminal domain of this protein is thought to mediate its association with SMG5 or UPF1 while the C-terminal domain interacts with the mRNA decay complex. This protein may therefore couple changes in UPF1 phosphorylation state to the degradation of NMD-candidate transcripts. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-183545018-A-G is Benign according to our data. Variant chr1-183545018-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2639628.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.23 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 837 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SMG7NM_001375584.1 linkuse as main transcriptc.2076A>G p.Pro692= synonymous_variant 16/23 ENST00000688051.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SMG7ENST00000688051.1 linkuse as main transcriptc.2076A>G p.Pro692= synonymous_variant 16/23 NM_001375584.1 P4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00551
AC:
837
AN:
151884
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000266
Gnomad AMI
AF:
0.0110
Gnomad AMR
AF:
0.000459
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0340
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00643
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00536
AC:
1348
AN:
251298
Hom.:
15
AF XY:
0.00520
AC XY:
706
AN XY:
135812
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.000434
Gnomad ASJ exome
AF:
0.00228
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0328
Gnomad NFE exome
AF:
0.00496
Gnomad OTH exome
AF:
0.00505
GnomAD4 exome
AF:
0.00365
AC:
5330
AN:
1461816
Hom.:
55
Cov.:
33
AF XY:
0.00363
AC XY:
2637
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.000313
Gnomad4 ASJ exome
AF:
0.00337
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0317
Gnomad4 NFE exome
AF:
0.00301
Gnomad4 OTH exome
AF:
0.00286
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00551
AC:
837
AN:
152002
Hom.:
11
Cov.:
32
AF XY:
0.00665
AC XY:
494
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.000266
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0340
Gnomad4 NFE
AF:
0.00643
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00575
Hom.:
5
Bravo
AF:
0.00217
EpiCase
AF:
0.00360
EpiControl
AF:
0.00267

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023SMG7: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
11
Dann
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs148022443; hg19: chr1-183514153; COSMIC: COSV61632700; COSMIC: COSV61632700; API