Variant rs2234694 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000454.5(SOD1):c.239+34A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 1,465,972 control chromosomes in the GnomAD database, including 1,443 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: 0.040 ( 1315 hom. )

Consequence

SOD1
NM_000454.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.14

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=-0.9).

BP6

Variant 21-31666552-A-C is Benign according to our data. Variant chr21-31666552-A-C is described in ClinVar as [Benign]. Clinvar id is 256202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0334 (5092/152278) while in subpopulation NFE AF= 0.0474 (3225/68020). AF 95% confidence interval is 0.046. There are 128 homozygotes in gnomad4. There are 2532 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.239+34A>C		intron_variant		ENST00000270142.11	NP_000445.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
SOD1	ENST00000270142.11 linkuse as main transcript	c.239+34A>C	intron_variant	1	NM_000454.5	ENSP00000270142	P1
SOD1	ENST00000389995.4 linkuse as main transcript	c.182+34A>C	intron_variant	3		ENSP00000374645
SOD1	ENST00000470944.1 linkuse as main transcript	n.1167+34A>C	intron_variant, non_coding_transcript_variant	2
SOD1	ENST00000476106.5 linkuse as main transcript	n.502+34A>C	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0335

AC:

5090

AN:

152160

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00833

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0202

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.0938

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0474

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0358

AC:

8654

AN:

241528

Hom.:

250

AF XY:

0.0360

AC XY:

4696

AN XY:

130346

show subpopulations

Gnomad AFR exome

AF:

0.00831

Gnomad AMR exome

AF:

0.0178

Gnomad ASJ exome

AF:

0.0208

Gnomad EAS exome

AF:

0.000831

Gnomad SAS exome

AF:

0.00968

Gnomad FIN exome

AF:

0.0907

Gnomad NFE exome

AF:

0.0486

Gnomad OTH exome

AF:

0.0420

GnomAD4 exome

AF:

0.0398

AC:

52266

AN:

1313694

Hom.:

1315

Cov.:

AF XY:

0.0390

AC XY:

25759

AN XY:

660966

show subpopulations

Gnomad4 AFR exome

AF:

0.00581

Gnomad4 AMR exome

AF:

0.0179

Gnomad4 ASJ exome

AF:

0.0210

Gnomad4 EAS exome

AF:

0.000282

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.0873

Gnomad4 NFE exome

AF:

0.0443

Gnomad4 OTH exome

AF:

0.0327

GnomAD4 genome

AF:

0.0334

AC:

5092

AN:

152278

Hom.:

128

Cov.:

AF XY:

0.0340

AC XY:

2532

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00830

Gnomad4 AMR

AF:

0.0202

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0104

Gnomad4 FIN

AF:

0.0938

Gnomad4 NFE

AF:

0.0474

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0409

Hom.:

Bravo

AF:

0.0271

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.050

DANN

Benign

0.37

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