dbSNP rs1044879: SMG7:c.*1686G>A (chr1-183553617-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001375584.1(SMG7):c.*1686G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 120,882 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000017 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SMG7
NM_001375584.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75

Publications

15 publications found

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]

SMG7 Gene-Disease associations (from GenCC):

autoimmune disease
Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

SMG7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375584.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMG7	NM_001375584.1	MANE Select	c.*1686G>A	3_prime_UTR	Exon 23 of 23	NP_001362513.1
SMG7	NM_001350220.2		c.*1686G>A	3_prime_UTR	Exon 25 of 25	NP_001337149.1
SMG7	NM_001394133.1		c.*1686G>A	3_prime_UTR	Exon 24 of 24	NP_001381062.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMG7	ENST00000688051.1	MANE Select	c.*1686G>A	3_prime_UTR	Exon 23 of 23	ENSP00000510175.1
SMG7	ENST00000507469.5	TSL:1	c.*416G>A	3_prime_UTR	Exon 23 of 23	ENSP00000425133.1
SMG7	ENST00000347615.6	TSL:1	c.*1686G>A	3_prime_UTR	Exon 22 of 22	ENSP00000340766.2

Frequencies

GnomAD3 genomes

AF:

0.0000166

AC:

AN:

120808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000287

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000185

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

9426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

4946

African (AFR)

AF:

0.00

AC:

AN:

238

American (AMR)

AF:

0.00

AC:

AN:

936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

218

East Asian (EAS)

AF:

0.00

AC:

AN:

256

South Asian (SAS)

AF:

0.00

AC:

AN:

1168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

5812

Other (OTH)

AF:

0.00

AC:

AN:

444

GnomAD4 genome

AF:

0.0000165

AC:

AN:

120882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

57686

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

36844

American (AMR)

AF:

0.00

AC:

AN:

10710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2860

East Asian (EAS)

AF:

0.000287

AC:

AN:

3480

South Asian (SAS)

AF:

0.00

AC:

AN:

3266

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.0000185

AC:

AN:

54042

Other (OTH)

AF:

0.00

AC:

AN:

1610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

304

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.51

(source)

DANN

Benign

0.75

PhyloP100

-1.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over