ENST00000545162.5:c.93-416C>G

Variant names:

• chr6-159693279-G-C
• rs5746092
• ENST00000545162.5:c.93-416C>G

Variant summary

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

The ENST00000545162.5(SOD2):​c.93-416C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 983,860 control chromosomes in the GnomAD database, including 28,464 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 (4223 hom., cov: 28)
  • Exomes 𝑓: 0.24 (24241 hom.)
• Consequence: SOD2 ENST00000545162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653
• Publications: 23 publications found

Genes affected

SOD2 (HGNC:11180): (superoxide dismutase 2) This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the superoxide byproducts of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), premature aging, sporadic motor neuron disease, and cancer. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 1. [provided by RefSeq, Apr 2016]

SOD2 Gene-Disease associations (from GenCC):

• cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000545162.5. 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
	SOD2	NM_001322817.2		c.-115-416C>G		intron	N/A	NP_001309746.1
	SOD2	NM_001322819.2		c.-115-416C>G		intron	N/A	NP_001309748.1
	SOD2	NM_001322820.2		c.-115-416C>G		intron	N/A	NP_001309749.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD2	ENST00000545162.5	TSL:3	c.93-416C>G		intron	N/A	ENSP00000441362.1
	SOD2	ENST00000535561.5	TSL:3	c.93-416C>G		intron	N/A	ENSP00000445015.1
	SOD2	ENST00000546087.5	TSL:2	c.-115-416C>G		intron	N/A	ENSP00000442920.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 34604 AN: 149370 Hom.: 4220 Cov.: 28

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0324

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.236 AC: 196881 AN: 834382 Hom.: 24241 Cov.: 11 AF XY: 0.238 AC XY: 102128 AN XY: 428674

African (AFR) AF: 0.179 AC: 3082 AN: 17244

American (AMR) AF: 0.204 AC: 5274 AN: 25844

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 3937 AN: 19392

East Asian (EAS) AF: 0.373 AC: 9322 AN: 24970

South Asian (SAS) AF: 0.254 AC: 15510 AN: 61168

European-Finnish (FIN) AF: 0.312 AC: 11091 AN: 35600

Middle Eastern (MID) AF: 0.284 AC: 838 AN: 2948

European-Non Finnish (NFE) AF: 0.228 AC: 138976 AN: 609394

Other (OTH) AF: 0.234 AC: 8851 AN: 37822

GnomAD4 genome AF: 0.232 AC: 34619 AN: 149478 Hom.: 4223 Cov.: 28 AF XY: 0.238 AC XY: 17375 AN XY: 72960

African (AFR) AF: 0.188 AC: 7674 AN: 40900

American (AMR) AF: 0.228 AC: 3434 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 697 AN: 3454

East Asian (EAS) AF: 0.394 AC: 1964 AN: 4986

South Asian (SAS) AF: 0.270 AC: 1296 AN: 4794

European-Finnish (FIN) AF: 0.332 AC: 3252 AN: 9804

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15716 AN: 67178

Other (OTH) AF: 0.237 AC: 494 AN: 2084

Alfa AF: 0.116 Hom.: 195

Bravo AF: 0.223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.4
DANN	Benign	0.24
PhyloP100		-0.65
PromoterAI		0.17	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
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: rs5746092; hg19: chr6-160114311;