rs2224770

Variant names:

• chr17-2302629-T-C
• rs2224770
• NM_017575.5:c.88+1004A>G

Variant summary

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

The NM_017575.5(SMG6):​c.88+1004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,086 control chromosomes in the GnomAD database, including 23,960 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 0.55 (23960 hom., cov: 33)
• Consequence: SMG6 NM_017575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 21 publications found

Genes affected

SMG6 (HGNC:17809): (SMG6 nonsense mediated mRNA decay factor) This gene encodes a component of the telomerase ribonucleoprotein complex responsible for the replication and maintenance of chromosome ends. The encoded protein also plays a role in the nonsense-mediated mRNA decay (NMD) pathway, providing the endonuclease activity near the premature translation termination codon that is needed to initiate NMD. Alternatively spliced transcript variants encoding distinct protein isoforms have been described. [provided by RefSeq, Feb 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMG6	NM_017575.5	c.88+1004A>G		intron_variant	Intron 1 of 18	ENST00000263073.11	NP_060045.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMG6	ENST00000263073.11	c.88+1004A>G		intron_variant	Intron 1 of 18	1	NM_017575.5	ENSP00000263073.5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83403 AN: 151968 Hom.: 23949 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.549 AC: 83447 AN: 152086 Hom.: 23960 Cov.: 33 AF XY: 0.553 AC XY: 41093 AN XY: 74342

African (AFR) AF: 0.370 AC: 15348 AN: 41450

American (AMR) AF: 0.597 AC: 9129 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2255 AN: 3470

East Asian (EAS) AF: 0.694 AC: 3598 AN: 5184

South Asian (SAS) AF: 0.551 AC: 2659 AN: 4826

European-Finnish (FIN) AF: 0.644 AC: 6800 AN: 10560

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41754 AN: 67990

Other (OTH) AF: 0.559 AC: 1180 AN: 2112

Alfa AF: 0.592 Hom.: 34014

Bravo AF: 0.539

Asia WGS AF: 0.556 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.9
DANN	Benign	0.51
PhyloP100		-0.31
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: rs2224770; hg19: chr17-2205923;