chr1-183483410-G-A

Variant names:

• chr1-183483410-G-A
• rs2702178
• NM_001375584.1:c.29+10761G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375584.1(SMG7):​c.29+10761G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,934 control chromosomes in the GnomAD database, including 9,528 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 (9528 hom., cov: 32)
• Consequence: SMG7 NM_001375584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG7	NM_001375584.1	MANE Select	c.29+10761G>A		intron	N/A	NP_001362513.1
	SMG7	NM_001350220.2		c.-161+10761G>A		intron	N/A	NP_001337149.1
	SMG7	NM_001394133.1		c.-24+10761G>A		intron	N/A	NP_001381062.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG7	ENST00000688051.1	MANE Select	c.29+10761G>A		intron	N/A	ENSP00000510175.1
	SMG7	ENST00000507469.5	TSL:1	c.29+10761G>A		intron	N/A	ENSP00000425133.1
	SMG7	ENST00000347615.6	TSL:1	c.29+10761G>A		intron	N/A	ENSP00000340766.2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53256 AN: 151816 Hom.: 9514 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.357

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.351 AC: 53303 AN: 151934 Hom.: 9528 Cov.: 32 AF XY: 0.354 AC XY: 26307 AN XY: 74256

African (AFR) AF: 0.275 AC: 11413 AN: 41466

American (AMR) AF: 0.402 AC: 6141 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1096 AN: 3460

East Asian (EAS) AF: 0.523 AC: 2702 AN: 5168

South Asian (SAS) AF: 0.409 AC: 1975 AN: 4828

European-Finnish (FIN) AF: 0.375 AC: 3950 AN: 10538

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24781 AN: 67902

Other (OTH) AF: 0.358 AC: 755 AN: 2106

Alfa AF: 0.329 Hom.: 3809

Bravo AF: 0.352

Asia WGS AF: 0.478 AC: 1655 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.3
DANN	Benign	0.67
PhyloP100		1.3
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: rs2702178; hg19: chr1-183452545;