16-18828350-A-T

Variant names:

• chr16-18828350-A-T
• rs904821
• NM_015092.5:c.9604-182T>A

Variant summary

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

The NM_015092.5(SMG1):​c.9604-182T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 152,066 control chromosomes in the GnomAD database, including 28,829 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 0.60 (28829 hom., cov: 32)
• Consequence: SMG1 NM_015092.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 7 publications found

Genes affected

SMG1 (HGNC:30045): (SMG1 nonsense mediated mRNA decay associated PI3K related kinase) This gene encodes a protein involved in nonsense-mediated mRNA decay (NMD) as part of the mRNA surveillance complex. The protein has kinase activity and is thought to function in NMD by phosphorylating the regulator of nonsense transcripts 1 protein. Alternatively spliced transcript variants have been described, but their full-length nature has yet to be determined. [provided by RefSeq, Mar 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015092.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG1	NM_015092.5	MANE Select	c.9604-182T>A		intron	N/A	NP_055907.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG1	ENST00000446231.7	TSL:1 MANE Select	c.9604-182T>A		intron	N/A	ENSP00000402515.3	Q96Q15-1
	SMG1	ENST00000565324.5	TSL:1	c.9274-182T>A		intron	N/A	ENSP00000456259.1	J3KRA9
	SMG1	ENST00000940395.1		c.9604-182T>A		intron	N/A	ENSP00000610454.1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91423 AN: 151948 Hom.: 28776 Cov.: 32

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.602 AC: 91534 AN: 152066 Hom.: 28829 Cov.: 32 AF XY: 0.595 AC XY: 44252 AN XY: 74326

African (AFR) AF: 0.790 AC: 32792 AN: 41506

American (AMR) AF: 0.560 AC: 8549 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2230 AN: 3466

East Asian (EAS) AF: 0.220 AC: 1140 AN: 5180

South Asian (SAS) AF: 0.480 AC: 2314 AN: 4818

European-Finnish (FIN) AF: 0.507 AC: 5361 AN: 10566

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37182 AN: 67968

Other (OTH) AF: 0.598 AC: 1259 AN: 2106

Alfa AF: 0.588 Hom.: 3293

Bravo AF: 0.612

Asia WGS AF: 0.415 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.031
DANN	Benign	0.33
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs904821; hg19: chr16-18839672;