Variant chr21-31667007-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000454.5(SOD1):c.240-251A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 542,660 control chromosomes in the GnomAD database, including 8,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 2061 hom., cov: 32)

Exomes 𝑓: 0.13 ( 6206 hom. )

Consequence

SOD1
NM_000454.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0290

Variant links:

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]

SOD1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 21-31667007-A-G is Benign according to our data. Variant chr21-31667007-A-G is described in ClinVar as [Benign]. Clinvar id is 1253758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOD1	NM_000454.5 linkuse as main transcript	c.240-251A>G		intron_variant		ENST00000270142.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOD1	ENST00000270142.11 linkuse as main transcript	c.240-251A>G		intron_variant		1	NM_000454.5	P1
	ENST00000609934.1 linkuse as main transcript	n.241T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20286

AN:

152086

Hom.:

2056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.0824

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.0993

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0651

Gnomad OTH

AF:

0.112

GnomAD4 exome

AF:

0.125

AC:

48871

AN:

390456

Hom.:

6206

Cov.:

AF XY:

0.126

AC XY:

26017

AN XY:

206944

show subpopulations

Gnomad4 AFR exome

AF:

0.175

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.0808

Gnomad4 EAS exome

AF:

0.524

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.0979

Gnomad4 NFE exome

AF:

0.0634

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.133

AC:

20318

AN:

152204

Hom.:

2061

Cov.:

AF XY:

0.138

AC XY:

10253

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.179

Gnomad4 AMR

AF:

0.205

Gnomad4 ASJ

AF:

0.0824

Gnomad4 EAS

AF:

0.514

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.0993

Gnomad4 NFE

AF:

0.0651

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.0850

Hom.:

905

Bravo

AF:

0.147

Asia WGS

AF:

0.332

AC:

1153

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.79

CADD

Benign

6.6

DANN

Benign

0.82

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over