chr1-183548836-T-C

Variant names:

• chr1-183548836-T-C
• rs2702180
• NM_001375584.1:c.2893-372T>C

Variant summary

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

The NM_001375584.1(SMG7):​c.2893-372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 187,470 control chromosomes in the GnomAD database, including 11,949 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 (9548 hom., cov: 32)
  • Exomes 𝑓: 0.35 (2401 hom.)
• Consequence: SMG7 NM_001375584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802
• Publications: 19 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 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.2893-372T>C		intron	N/A	NP_001362513.1
	SMG7	NM_001350220.2		c.2980-372T>C		intron	N/A	NP_001337149.1
	SMG7	NM_001394133.1		c.2980-372T>C		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.2893-372T>C		intron	N/A	ENSP00000510175.1
	SMG7	ENST00000507469.5	TSL:1	c.2755-372T>C		intron	N/A	ENSP00000425133.1
	SMG7	ENST00000347615.6	TSL:1	c.2743-372T>C		intron	N/A	ENSP00000340766.2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53329 AN: 151938 Hom.: 9533 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.354 AC: 12554 AN: 35414 Hom.: 2401 AF XY: 0.354 AC XY: 6467 AN XY: 18288

African (AFR) AF: 0.255 AC: 302 AN: 1186

American (AMR) AF: 0.424 AC: 1091 AN: 2576

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 411 AN: 1366

East Asian (EAS) AF: 0.509 AC: 1026 AN: 2016

South Asian (SAS) AF: 0.343 AC: 666 AN: 1940

European-Finnish (FIN) AF: 0.363 AC: 478 AN: 1318

Middle Eastern (MID) AF: 0.274 AC: 40 AN: 146

European-Non Finnish (NFE) AF: 0.344 AC: 7775 AN: 22624

Other (OTH) AF: 0.341 AC: 765 AN: 2242

GnomAD4 genome AF: 0.351 AC: 53376 AN: 152056 Hom.: 9548 Cov.: 32 AF XY: 0.354 AC XY: 26347 AN XY: 74332

African (AFR) AF: 0.275 AC: 11424 AN: 41470

American (AMR) AF: 0.402 AC: 6150 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2714 AN: 5178

South Asian (SAS) AF: 0.409 AC: 1968 AN: 4814

European-Finnish (FIN) AF: 0.374 AC: 3956 AN: 10566

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

European-Non Finnish (NFE) AF: 0.365 AC: 24819 AN: 67960

Other (OTH) AF: 0.358 AC: 756 AN: 2110

Alfa AF: 0.336 Hom.: 4526

Bravo AF: 0.353

Asia WGS AF: 0.477 AC: 1660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.62
PhyloP100		-0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2702180; hg19: chr1-183517971;