Genetic Variant SMG7:c.2893-372T>C (chr1-183548836-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001375584.1(SMG7):c.2893-372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 187,470 control chromosomes in the GnomAD database, including 11,949 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 ( 9548 hom., cov: 32)

Exomes 𝑓: 0.35 ( 2401 hom. )

Consequence

SMG7
NM_001375584.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.802

Publications

19 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMG7	NM_001375584.1 link	c.2893-372T>C		intron_variant	Intron 18 of 22	ENST00000688051.1	NP_001362513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMG7	ENST00000688051.1 link	c.2893-372T>C		intron_variant	Intron 18 of 22		NM_001375584.1	ENSP00000510175.1

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53329

AN:

151938

Hom.:

9533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.374

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.356

GnomAD4 exome

AF:

0.354

AC:

12554

AN:

35414

Hom.:

2401

AF XY:

0.354

AC XY:

6467

AN XY:

18288

show subpopulations

African (AFR)

AF:

0.255

AC:

302

AN:

1186

American (AMR)

AF:

0.424

AC:

1091

AN:

2576

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

411

AN:

1366

East Asian (EAS)

AF:

0.509

AC:

1026

AN:

2016

South Asian (SAS)

AF:

0.343

AC:

666

AN:

1940

European-Finnish (FIN)

AF:

0.363

AC:

478

AN:

1318

Middle Eastern (MID)

AF:

0.274

AC:

AN:

146

European-Non Finnish (NFE)

AF:

0.344

AC:

7775

AN:

22624

Other (OTH)

AF:

0.341

AC:

765

AN:

2242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

400

799

1199

1598

1998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.351

AC:

53376

AN:

152056

Hom.:

9548

Cov.:

AF XY:

0.354

AC XY:

26347

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.275

AC:

11424

AN:

41470

American (AMR)

AF:

0.402

AC:

6150

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.317

AC:

1099

AN:

3468

East Asian (EAS)

AF:

0.524

AC:

2714

AN:

5178

South Asian (SAS)

AF:

0.409

AC:

1968

AN:

4814

European-Finnish (FIN)

AF:

0.374

AC:

3956

AN:

10566

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.365

AC:

24819

AN:

67960

Other (OTH)

AF:

0.358

AC:

756

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1796

3592

5388

7184

8980

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:

0.336

Hom.:

4526

Bravo

AF:

0.353

Asia WGS

AF:

0.477

AC:

1660

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.77

(source)

DANN

Benign

0.62

PhyloP100

-0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over