rs4516970

Variant names:

• chr6-159716655-G-A
• rs4516970
• ENST00000545162.5:c.92+10611C>T

Variant summary

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

The ENST00000545162.5(SOD2):​c.92+10611C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 152,212 control chromosomes in the GnomAD database, including 388 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 0.054 (388 hom., cov: 32)
• Consequence: SOD2 ENST00000545162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 21 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOD2	NM_001322817.2	c.-116+14230C>T		intron_variant	Intron 3 of 7		NP_001309746.1
SOD2	NM_001322819.2	c.-116+10611C>T		intron_variant	Intron 1 of 4		NP_001309748.1
SOD2	NM_001322820.2	c.-116+10197C>T		intron_variant	Intron 1 of 4		NP_001309749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000545162.5	c.92+10611C>T		intron_variant	Intron 1 of 3	3		ENSP00000441362.1
SOD2	ENST00000535561.5	c.92+10197C>T		intron_variant	Intron 1 of 3	3		ENSP00000445015.1
SOD2	ENST00000546087.5	c.-116+14230C>T		intron_variant	Intron 3 of 7	2		ENSP00000442920.1

Frequencies

GnomAD3 genomes AF: 0.0535 AC: 8137 AN: 152094 Hom.: 386 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0427

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0567

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

GnomAD4 genome AF: 0.0536 AC: 8160 AN: 152212 Hom.: 388 Cov.: 32 AF XY: 0.0532 AC XY: 3960 AN XY: 74420

African (AFR) AF: 0.120 AC: 4962 AN: 41520

American (AMR) AF: 0.0426 AC: 651 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0661 AC: 319 AN: 4826

European-Finnish (FIN) AF: 0.0191 AC: 203 AN: 10610

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0259 AC: 1763 AN: 68020

Other (OTH) AF: 0.0561 AC: 118 AN: 2104

Alfa AF: 0.0358 Hom.: 738

Bravo AF: 0.0574

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.75
DANN	Benign	0.54
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4516970; hg19: chr6-160137687;