chr1-183525318-G-A

Variant names:

• chr1-183525318-G-A
• rs6662844
• NM_001375584.1:c.313-1278G>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.313-1278G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,916 control chromosomes in the GnomAD database, including 20,109 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 0.51 (20109 hom., cov: 31)
• Consequence: SMG7 NM_001375584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• Publications: 13 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMG7	NM_001375584.1	c.313-1278G>A		intron_variant	Intron 4 of 22	ENST00000688051.1	NP_001362513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMG7	ENST00000688051.1	c.313-1278G>A		intron_variant	Intron 4 of 22		NM_001375584.1	ENSP00000510175.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77822 AN: 151798 Hom.: 20078 Cov.: 31

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.513 AC: 77897 AN: 151916 Hom.: 20109 Cov.: 31 AF XY: 0.515 AC XY: 38208 AN XY: 74236

African (AFR) AF: 0.544 AC: 22530 AN: 41418

American (AMR) AF: 0.581 AC: 8869 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1379 AN: 3470

East Asian (EAS) AF: 0.649 AC: 3352 AN: 5162

South Asian (SAS) AF: 0.511 AC: 2467 AN: 4826

European-Finnish (FIN) AF: 0.487 AC: 5132 AN: 10546

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32490 AN: 67934

Other (OTH) AF: 0.500 AC: 1057 AN: 2112

Alfa AF: 0.487 Hom.: 31426

Bravo AF: 0.524

Asia WGS AF: 0.587 AC: 2040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.46
DANN	Benign	0.40
PhyloP100		-0.14
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: rs6662844; hg19: chr1-183494453;