chr21-31664078-T-G

Position:

• chr21-31664078-T-G

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.169+192T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,086 control chromosomes in the GnomAD database, including 3,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3603 hom., cov: 32)
• Consequence: SOD1 NM_000454.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.670

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=-0.94).
• BP6: Variant 21-31664078-T-G is Benign according to our data. Variant chr21-31664078-T-G is described in ClinVar as [Benign]. Clinvar id is 1222120.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOD1	NM_000454.5	c.169+192T>G		intron_variant		ENST00000270142.11	NP_000445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOD1	ENST00000270142.11	c.169+192T>G		intron_variant		1	NM_000454.5	ENSP00000270142	P1
SOD1	ENST00000389995.4	c.112+192T>G		intron_variant		3		ENSP00000374645
SOD1	ENST00000470944.1	n.1097+192T>G		intron_variant, non_coding_transcript_variant		2
SOD1	ENST00000476106.5	n.432+192T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29365 AN: 151968 Hom.: 3585 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.193 AC: 29422 AN: 152086 Hom.: 3603 Cov.: 32 AF XY: 0.198 AC XY: 14727 AN XY: 74358

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.0974

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.155

Alfa AF: 0.0722 Hom.: 78

Bravo AF: 0.204

Asia WGS AF: 0.348 AC: 1211 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	-0.94
CADD	Benign	4.7
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10432782; hg19: chr21-33036391;