1-183553617-G-C

Position:

• chr1-183553617-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375584.1(SMG7):​c.*1686G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 120,336 control chromosomes in the GnomAD database, including 3,253 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 0.18 (3229 hom., cov: 25)
  • Exomes 𝑓: 0.064 (24 hom.)
• Consequence: SMG7 NM_001375584.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMG7	NM_001375584.1	c.*1686G>C		3_prime_UTR_variant	23/23	ENST00000688051.1	NP_001362513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG7	ENST00000688051.1	c.*1686G>C		3_prime_UTR_variant	23/23		NM_001375584.1	ENSP00000510175.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 19699 AN: 110970 Hom.: 3232 Cov.: 25

Gnomad AFR AF: 0.0670

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.0637 AC: 592 AN: 9300 Hom.: 24 Cov.: 0 AF XY: 0.0639 AC XY: 312 AN XY: 4882

Gnomad4 AFR exome AF: 0.00420

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.0505

Gnomad4 EAS exome AF: 0.0669

Gnomad4 SAS exome AF: 0.0526

Gnomad4 FIN exome AF: 0.0309

Gnomad4 NFE exome AF: 0.0617

Gnomad4 OTH exome AF: 0.0518

GnomAD4 genome AF: 0.177 AC: 19684 AN: 111036 Hom.: 3229 Cov.: 25 AF XY: 0.165 AC XY: 8757 AN XY: 52922

Gnomad4 AFR AF: 0.0668

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.165

Alfa AF: 0.117 Hom.: 304

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.17

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

Other links and lift over

dbSNP: rs1044879; hg19: chr1-183522752; COSMIC: COSV61630259; COSMIC: COSV61630259;