rs5746151

Variant names:

• chr6-159680288-C-T
• rs5746151
• NM_000636.4:c.*2205G>A

Variant summary

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

The NM_000636.4(SOD2):​c.*2205G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 152,144 control chromosomes in the GnomAD database, including 265 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 0.055 (265 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SOD2 NM_000636.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• Publications: 24 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_000636.4	c.*2205G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000538183.7	NP_000627.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000538183.7	c.*2205G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_000636.4	ENSP00000446252.1

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8316 AN: 152026 Hom.: 265 Cov.: 32

Gnomad AFR AF: 0.0476

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.0739

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0592

Gnomad OTH AF: 0.0606

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0547 AC: 8325 AN: 152144 Hom.: 265 Cov.: 32 AF XY: 0.0549 AC XY: 4082 AN XY: 74370

African (AFR) AF: 0.0477 AC: 1979 AN: 41496

American (AMR) AF: 0.0659 AC: 1006 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0739 AC: 256 AN: 3464

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5180

South Asian (SAS) AF: 0.0708 AC: 342 AN: 4828

European-Finnish (FIN) AF: 0.0419 AC: 444 AN: 10586

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0592 AC: 4024 AN: 68000

Other (OTH) AF: 0.0600 AC: 127 AN: 2116

Alfa AF: 0.0562 Hom.: 403

Bravo AF: 0.0541

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		-0.37
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: rs5746151; hg19: chr6-160101320;