rs5746094

Variant names:

• chr6-159693136-T-C
• rs5746094
• NM_000636.4:c.23+9A>G

Variant summary

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

The NM_000636.4(SOD2):​c.23+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,529,256 control chromosomes in the GnomAD database, including 45,599 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 (4232 hom., cov: 31)
  • Exomes 𝑓: 0.24 (41367 hom.)
• Consequence: SOD2 NM_000636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 15 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):

• microvascular complications of diabetes, susceptibility to, 6

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
• cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000636.4. 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
	SOD2	NM_000636.4	MANE Select	c.23+9A>G		intron	N/A	NP_000627.2	P04179-1
	SOD2	NM_001024465.3		c.23+9A>G		intron	N/A	NP_001019636.1	P04179-1
	SOD2	NM_001024466.3		c.23+9A>G		intron	N/A	NP_001019637.1	P04179-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD2	ENST00000538183.7	TSL:1 MANE Select	c.23+9A>G		intron	N/A	ENSP00000446252.1	P04179-1
	SOD2	ENST00000367055.8	TSL:1	c.23+9A>G		intron	N/A	ENSP00000356022.4	P04179-1
	SOD2	ENST00000452684.2	TSL:1	c.23+9A>G		intron	N/A	ENSP00000406713.2	G5E9P6

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35168 AN: 151666 Hom.: 4230 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.238

GnomAD2 exomes AF: 0.247 AC: 32795 AN: 132636 AF XY: 0.248

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.201

Gnomad ASJ exome AF: 0.205

Gnomad EAS exome AF: 0.381

Gnomad FIN exome AF: 0.320

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.240

GnomAD4 exome AF: 0.242 AC: 333911 AN: 1377482 Hom.: 41367 Cov.: 33 AF XY: 0.244 AC XY: 165871 AN XY: 679418

African (AFR) AF: 0.180 AC: 5224 AN: 28956

American (AMR) AF: 0.209 AC: 7035 AN: 33720

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 5026 AN: 24464

East Asian (EAS) AF: 0.376 AC: 12492 AN: 33210

South Asian (SAS) AF: 0.258 AC: 19891 AN: 76978

European-Finnish (FIN) AF: 0.313 AC: 15036 AN: 48012

Middle Eastern (MID) AF: 0.284 AC: 1265 AN: 4458

European-Non Finnish (NFE) AF: 0.237 AC: 254193 AN: 1070624

Other (OTH) AF: 0.241 AC: 13749 AN: 57060

GnomAD4 genome AF: 0.232 AC: 35182 AN: 151774 Hom.: 4232 Cov.: 31 AF XY: 0.239 AC XY: 17694 AN XY: 74164

African (AFR) AF: 0.188 AC: 7777 AN: 41422

American (AMR) AF: 0.227 AC: 3461 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3464

East Asian (EAS) AF: 0.397 AC: 2031 AN: 5122

South Asian (SAS) AF: 0.270 AC: 1303 AN: 4820

European-Finnish (FIN) AF: 0.329 AC: 3458 AN: 10516

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15859 AN: 67840

Other (OTH) AF: 0.237 AC: 501 AN: 2110

Alfa AF: 0.232 Hom.: 3625

Bravo AF: 0.223

Asia WGS AF: 0.301 AC: 1039 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.8
DANN	Benign	0.43
PhyloP100		0.20
PromoterAI		0.017	Neutral
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: rs5746094; hg19: chr6-160114168; COSMIC: COSV61623032; COSMIC: COSV61623032;