chr1-183553617-G-C

Variant names:

• chr1-183553617-G-C
• rs1044879
• NM_001375584.1:c.*1686G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

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. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. 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
• Publications: 15 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).

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

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

Ensembl Transcripts

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

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00420 AC: 1 AN: 238

American (AMR) AF: 0.125 AC: 114 AN: 910

Ashkenazi Jewish (ASJ) AF: 0.0505 AC: 11 AN: 218

East Asian (EAS) AF: 0.0669 AC: 17 AN: 254

South Asian (SAS) AF: 0.0526 AC: 61 AN: 1160

European-Finnish (FIN) AF: 0.0309 AC: 10 AN: 324

Middle Eastern (MID) AF: 0.0667 AC: 2 AN: 30

European-Non Finnish (NFE) AF: 0.0617 AC: 353 AN: 5722

Other (OTH) AF: 0.0518 AC: 23 AN: 444

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0668 AC: 2374 AN: 35548

American (AMR) AF: 0.193 AC: 1836 AN: 9536

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 543 AN: 2580

East Asian (EAS) AF: 0.362 AC: 1115 AN: 3084

South Asian (SAS) AF: 0.205 AC: 612 AN: 2988

European-Finnish (FIN) AF: 0.145 AC: 931 AN: 6426

Middle Eastern (MID) AF: 0.123 AC: 27 AN: 220

European-Non Finnish (NFE) AF: 0.243 AC: 11807 AN: 48624

Other (OTH) AF: 0.165 AC: 238 AN: 1440

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.117 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	0.20
DANN	Benign	0.17
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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