rs1041740

chr21-31667849-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000454.5(SOD1):c.357+474C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,118 control chromosomes in the GnomAD database, including 5,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5471 hom., cov: 32)
• Consequence: SOD1 NM_000454.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.455

Genes affected

SOD1 (HGNC:11179): (superoxide dismutase 1) The protein encoded by this gene binds copper and zinc ions and is one of two isozymes responsible for destroying free superoxide radicals in the body. The encoded isozyme is a soluble cytoplasmic protein, acting as a homodimer to convert naturally-occuring but harmful superoxide radicals to molecular oxygen and hydrogen peroxide. The other isozyme is a mitochondrial protein. In addition, this protein contains an antimicrobial peptide that displays antibacterial, antifungal, and anti-MRSA activity against E. coli, E. faecalis, S. aureus, S. aureus MRSA LPV+, S. agalactiae, and yeast C. krusei. Mutations in this gene have been implicated as causes of familial amyotrophic lateral sclerosis. Rare transcript variants have been reported for this gene. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 21-31667849-C-T is Benign according to our data. Variant chr21-31667849-C-T is described in ClinVar as [Benign]. Clinvar id is 1261166.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD1	NM_000454.5	c.357+474C>T		intron_variant		ENST00000270142.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD1	ENST00000270142.11	c.357+474C>T		intron_variant		1	NM_000454.5	P1
SOD1	ENST00000389995.4	c.300+474C>T		intron_variant		3
SOD1	ENST00000470944.1	n.1285+474C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37857 AN: 152000 Hom.: 5466 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.249 AC: 37858 AN: 152118 Hom.: 5471 Cov.: 32 AF XY: 0.251 AC XY: 18637 AN XY: 74348

Gnomad4 AFR AF: 0.0999

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.283

Alfa AF: 0.304 Hom.: 14793

Bravo AF: 0.250

Asia WGS AF: 0.274 AC: 951 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.1
Dann	Benign	0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs1041740; hg19: chr21-33040162;