rs2758357

Positions:

• chr6-159713959-C-T

Variant summary

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

The NM_001322817.2(SOD2):​c.-116+16926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 790,188 control chromosomes in the GnomAD database, including 67,318 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 0.40 (13691 hom., cov: 30)
  • Exomes 𝑓: 0.39 (53627 hom.)
• Consequence: SOD2 NM_001322817.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

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]

HNRNPH1P1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD2	NM_001322817.2	c.-116+16926G>A		intron_variant			NP_001309746.1
SOD2	NM_001322819.2	c.-116+13307G>A		intron_variant			NP_001309748.1
SOD2	NM_001322820.2	c.-116+12893G>A		intron_variant			NP_001309749.1
HNRNPH1P1		n.159713959C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD2	ENST00000545162.5	c.92+13307G>A		intron_variant		3		ENSP00000441362.1
SOD2	ENST00000535561.5	c.92+12893G>A		intron_variant		3		ENSP00000445015.1
SOD2	ENST00000546087.5	c.-116+16926G>A		intron_variant		2		ENSP00000442920.1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61277 AN: 151674 Hom.: 13684 Cov.: 30

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.390 AC: 248900 AN: 638396 Hom.: 53627 Cov.: 8 AF XY: 0.396 AC XY: 132096 AN XY: 333888

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.573

Gnomad4 ASJ exome AF: 0.443

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.395

GnomAD4 genome AF: 0.404 AC: 61279 AN: 151792 Hom.: 13691 Cov.: 30 AF XY: 0.402 AC XY: 29847 AN XY: 74158

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.417

Alfa AF: 0.453 Hom.: 2052

Bravo AF: 0.397

Asia WGS AF: 0.332 AC: 1154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.3
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2758357; hg19: chr6-160134991; COSMIC: COSV67835003;