rs16988404

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000454.5(SOD1):c.73-108T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 859,572 control chromosomes in the GnomAD database, including 846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 128 hom., cov: 32)

Exomes 𝑓: 0.039 ( 718 hom. )

Consequence

SOD1
NM_000454.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.159

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 21-31663682-T-A is Benign according to our data. Variant chr21-31663682-T-A is described in ClinVar as [Benign]. Clinvar id is 440292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-31663682-T-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0334 (5090/152250) while in subpopulation NFE AF= 0.0474 (3223/68002). AF 95% confidence interval is 0.046. There are 128 homozygotes in gnomad4. There are 2533 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 128 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD1	NM_000454.5 linkuse as main transcript	c.73-108T>A		intron_variant		ENST00000270142.11	NP_000445.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
SOD1	ENST00000270142.11 linkuse as main transcript	c.73-108T>A	intron_variant	1	NM_000454.5	ENSP00000270142	P1
SOD1	ENST00000389995.4 linkuse as main transcript	c.16-108T>A	intron_variant	3		ENSP00000374645
SOD1	ENST00000470944.1 linkuse as main transcript	n.1001-108T>A	intron_variant, non_coding_transcript_variant	2
SOD1	ENST00000476106.5 linkuse as main transcript	n.336-108T>A	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0334

AC:

5088

AN:

152132

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00821

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.0939

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0474

Gnomad OTH

AF:

0.0268

GnomAD4 exome

AF:

0.0388

AC:

27465

AN:

707322

Hom.:

718

AF XY:

0.0375

AC XY:

14094

AN XY:

375638

show subpopulations

Gnomad4 AFR exome

AF:

0.00649

Gnomad4 AMR exome

AF:

0.0182

Gnomad4 ASJ exome

AF:

0.0206

Gnomad4 EAS exome

AF:

0.000253

Gnomad4 SAS exome

AF:

0.00996

Gnomad4 FIN exome

AF:

0.0875

Gnomad4 NFE exome

AF:

0.0453

Gnomad4 OTH exome

AF:

0.0346

GnomAD4 genome

AF:

0.0334

AC:

5090

AN:

152250

Hom.:

128

Cov.:

AF XY:

0.0340

AC XY:

2533

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00818

Gnomad4 AMR

AF:

0.0203

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0104

Gnomad4 FIN

AF:

0.0939

Gnomad4 NFE

AF:

0.0474

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0174

Hom.:

Bravo

AF:

0.0271

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	This variant is associated with the following publications: (PMID: 16036425, 9462467, 9786240) -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Dec 09, 2019	- -

Amyotrophic lateral sclerosis type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.0

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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