rs10911353

Variant names:

• chr1-183520068-G-A
• rs10911353
• NM_001375584.1:c.312+2248G>A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMG7	NM_001375584.1	c.312+2248G>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.312+2248G>A		intron_variant	Intron 4 of 22		NM_001375584.1	ENSP00000510175.1

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

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.337

Alfa AF: 0.351 Hom.: 4530

Bravo AF: 0.315

Asia WGS AF: 0.467 AC: 1607 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.58

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: rs10911353; hg19: chr1-183489203;