chr6-159761064-A-G

Variant names:

• chr6-159761064-A-G
• rs927450
• ENST00000535372.1:n.912T>C

Variant summary

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

The ENST00000535372.1(SOD2-OT1):​n.912T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 153,446 control chromosomes in the GnomAD database, including 18,128 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 0.46 (17953 hom., cov: 32)
  • Exomes 𝑓: 0.43 (175 hom.)
• Consequence: SOD2-OT1 ENST00000535372.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 22 publications found

Genes affected

SOD2-OT1 (HGNC:53445): (SOD2 overlapping transcript 1)

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000535372.1. 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-OT1	NR_037166.1		n.912T>C		non_coding_transcript_exon	Exon 2 of 2
	SOD2	NM_001322817.2		c.-363T>C		5_prime_UTR	Exon 1 of 8	NP_001309746.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD2-OT1	ENST00000535372.1	TSL:1	n.912T>C		non_coding_transcript_exon	Exon 2 of 2
	SOD2	ENST00000546087.5	TSL:2	c.-363T>C		5_prime_UTR	Exon 1 of 8	ENSP00000442920.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69283 AN: 151944 Hom.: 17947 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.434 AC: 601 AN: 1384 Hom.: 175 Cov.: 0 AF XY: 0.441 AC XY: 377 AN XY: 854

African (AFR) AF: 0.227 AC: 5 AN: 22

American (AMR) AF: 0.550 AC: 22 AN: 40

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 8 AN: 14

East Asian (EAS) AF: 0.0500 AC: 1 AN: 20

South Asian (SAS) AF: 0.412 AC: 197 AN: 478

European-Finnish (FIN) AF: 0.444 AC: 16 AN: 36

Middle Eastern (MID) AF: 0.500 AC: 2 AN: 4

European-Non Finnish (NFE) AF: 0.450 AC: 316 AN: 702

Other (OTH) AF: 0.500 AC: 34 AN: 68

GnomAD4 genome AF: 0.456 AC: 69282 AN: 152062 Hom.: 17953 Cov.: 32 AF XY: 0.454 AC XY: 33755 AN XY: 74322

African (AFR) AF: 0.219 AC: 9082 AN: 41480

American (AMR) AF: 0.543 AC: 8301 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1957 AN: 3472

East Asian (EAS) AF: 0.178 AC: 920 AN: 5166

South Asian (SAS) AF: 0.495 AC: 2383 AN: 4816

European-Finnish (FIN) AF: 0.562 AC: 5930 AN: 10554

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39152 AN: 67984

Other (OTH) AF: 0.456 AC: 964 AN: 2112

Alfa AF: 0.538 Hom.: 36224

Bravo AF: 0.443

Asia WGS AF: 0.349 AC: 1214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.82
PhyloP100		-0.15
Mutation Taster		=294/6	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: rs927450; hg19: chr6-160182096;