chr6-159693540-G-T

Position:

• chr6-159693540-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001322817.2(SOD2):​c.-115-677C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,004 control chromosomes in the GnomAD database, including 16,037 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 0.45 (16037 hom., cov: 33)
• Consequence: SOD2 NM_001322817.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.743

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD2	NM_001322817.2	c.-115-677C>A		intron_variant			NP_001309746.1
SOD2	NM_001322819.2	c.-115-677C>A		intron_variant			NP_001309748.1
SOD2	NM_001322820.2	c.-115-677C>A		intron_variant			NP_001309749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000545162.5	c.93-677C>A		intron_variant		3		ENSP00000441362.1
SOD2	ENST00000535561.5	c.93-677C>A		intron_variant		3		ENSP00000445015.1
SOD2	ENST00000546087.5	c.-115-677C>A		intron_variant		2		ENSP00000442920.1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68327 AN: 151888 Hom.: 16024 Cov.: 33

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.450 AC: 68364 AN: 152004 Hom.: 16037 Cov.: 33 AF XY: 0.446 AC XY: 33116 AN XY: 74294

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.452

Alfa AF: 0.354 Hom.: 973

Bravo AF: 0.448

Asia WGS AF: 0.341 AC: 1184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.1
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2758343; hg19: chr6-160114572;