rs10911353

Variant names:

• chr1-183520068-G-A
• rs10911353
• NM_001375584.1:c.312+2248G>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.312+2248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 150,990 control chromosomes in the GnomAD database, including 8,374 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 0.32 (8374 hom., cov: 31)
• Consequence: SMG7 NM_001375584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.984
• Publications: 17 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=-0.9).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG7	NM_001375584.1	MANE Select	c.312+2248G>A		intron	N/A	NP_001362513.1
	SMG7	NM_001350220.2		c.399+2248G>A		intron	N/A	NP_001337149.1
	SMG7	NM_001394133.1		c.399+2248G>A		intron	N/A	NP_001381062.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG7	ENST00000688051.1	MANE Select	c.312+2248G>A		intron	N/A	ENSP00000510175.1
	SMG7	ENST00000507469.5	TSL:1	c.312+2248G>A		intron	N/A	ENSP00000425133.1
	SMG7	ENST00000347615.6	TSL:1	c.312+2248G>A		intron	N/A	ENSP00000340766.2

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48018 AN: 150884 Hom.: 8364 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.276

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.318 AC: 48046 AN: 150990 Hom.: 8374 Cov.: 31 AF XY: 0.323 AC XY: 23795 AN XY: 73686

African (AFR) AF: 0.162 AC: 6669 AN: 41172

American (AMR) AF: 0.390 AC: 5911 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1096 AN: 3466

East Asian (EAS) AF: 0.523 AC: 2688 AN: 5144

South Asian (SAS) AF: 0.409 AC: 1959 AN: 4794

European-Finnish (FIN) AF: 0.375 AC: 3820 AN: 10176

Middle Eastern (MID) AF: 0.276 AC: 79 AN: 286

European-Non Finnish (NFE) AF: 0.365 AC: 24717 AN: 67780

Other (OTH) AF: 0.337 AC: 704 AN: 2090

Alfa AF: 0.331 Hom.: 7888

Bravo AF: 0.315

Asia WGS AF: 0.467 AC: 1607 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.58
PhyloP100		-0.98
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: rs10911353; hg19: chr1-183489203;