16-18848659-G-T

Position:

• chr16-18848659-G-T

Variant summary

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

The NM_015092.5(SMG1):​c.5623+558C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,476 control chromosomes in the GnomAD database, including 28,623 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 (28623 hom., cov: 28)
• Consequence: SMG1 NM_015092.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMG1	NM_015092.5	c.5623+558C>A		intron_variant		ENST00000446231.7	NP_055907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG1	ENST00000446231.7	c.5623+558C>A		intron_variant		1	NM_015092.5	ENSP00000402515.3
SMG1	ENST00000565324.5	c.5293+558C>A		intron_variant		1		ENSP00000456259.1
SMG1	ENST00000562668.1	n.154+558C>A		intron_variant		3
SMG1	ENST00000563448.1	n.465+558C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.601 AC: 90951 AN: 151358 Hom.: 28570 Cov.: 28

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.601 AC: 91062 AN: 151476 Hom.: 28623 Cov.: 28 AF XY: 0.595 AC XY: 43977 AN XY: 73970

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.595

Alfa AF: 0.595 Hom.: 3977

Bravo AF: 0.611

Asia WGS AF: 0.412 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2925508; hg19: chr16-18859981;