1-156276937-T-G

Position:

• chr1-156276937-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015327.3(SMG5):​c.454+148A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 751,488 control chromosomes in the GnomAD database, including 18,873 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 0.21 (3697 hom., cov: 32)
  • Exomes 𝑓: 0.22 (15176 hom.)
• Consequence: SMG5 NM_015327.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524

Genes affected

SMG5 (HGNC:24644): (SMG5 nonsense mediated mRNA decay factor) SMG5 is involved in nonsense-mediated mRNA decay (Ohnishi et al., 2003 [PubMed 14636577]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMG5	NM_015327.3	c.454+148A>C		intron_variant		ENST00000361813.5	NP_056142.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG5	ENST00000361813.5	c.454+148A>C		intron_variant		1	NM_015327.3	ENSP00000355261	P1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32417 AN: 152126 Hom.: 3679 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.217 AC: 130089 AN: 599244 Hom.: 15176 AF XY: 0.219 AC XY: 66913 AN XY: 305634

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.251

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.220

GnomAD4 genome AF: 0.213 AC: 32465 AN: 152244 Hom.: 3697 Cov.: 32 AF XY: 0.213 AC XY: 15838 AN XY: 74440

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.229

Alfa AF: 0.221 Hom.: 7907

Bravo AF: 0.228

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.69

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: rs2277872; hg19: chr1-156246728;