1-156249119-C-G

Variant names:

• chr1-156249119-C-G
• rs2241106
• NM_015327.3:c.*1468G>C

Variant summary

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

The NM_015327.3(SMG5):​c.*1468G>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 156,366 control chromosomes in the GnomAD database, including 4,641 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 0.23 (4549 hom., cov: 32)
  • Exomes 𝑓: 0.20 (92 hom.)
• Consequence: SMG5 NM_015327.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015327.3. 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
	SMG5	NM_015327.3	MANE Select	c.*1468G>C		downstream_gene	N/A	NP_056142.2
	SMG5	NM_001323615.2		c.*1468G>C		downstream_gene	N/A	NP_001310544.1
	SMG5	NM_001323614.2		c.*1468G>C		downstream_gene	N/A	NP_001310543.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG5	ENST00000361813.5	TSL:1 MANE Select	c.*1468G>C		downstream_gene	N/A	ENSP00000355261.5

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34375 AN: 152084 Hom.: 4551 Cov.: 32

Gnomad AFR AF: 0.0903

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.197 AC: 821 AN: 4164 Hom.: 92 AF XY: 0.194 AC XY: 418 AN XY: 2158

African (AFR) AF: 0.0417 AC: 1 AN: 24

American (AMR) AF: 0.185 AC: 196 AN: 1060

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 3 AN: 8

East Asian (EAS) AF: 0.116 AC: 10 AN: 86

South Asian (SAS) AF: 0.111 AC: 42 AN: 378

European-Finnish (FIN) AF: 0.105 AC: 4 AN: 38

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.220 AC: 531 AN: 2414

Other (OTH) AF: 0.221 AC: 34 AN: 154

GnomAD4 genome AF: 0.226 AC: 34360 AN: 152202 Hom.: 4549 Cov.: 32 AF XY: 0.227 AC XY: 16912 AN XY: 74414

African (AFR) AF: 0.0900 AC: 3741 AN: 41548

American (AMR) AF: 0.256 AC: 3911 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1080 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1188 AN: 5180

South Asian (SAS) AF: 0.224 AC: 1081 AN: 4822

European-Finnish (FIN) AF: 0.287 AC: 3047 AN: 10602

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19369 AN: 67974

Other (OTH) AF: 0.241 AC: 510 AN: 2114

Alfa AF: 0.261 Hom.: 763

Bravo AF: 0.217

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.3
DANN	Benign	0.85
PhyloP100		-0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2241106; hg19: chr1-156218910;