rs7277748

Variant names:

• chr21-31659661-A-G
• rs7277748
• ENST00000928717.1:c.-109A>G

Your query was ambiguous. Multiple possible variants found:

• chr21-31659661-A-G
• chr21-31659661-A-C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000928717.1(SOD1):​c.-109A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00869 in 1,183,742 control chromosomes in the GnomAD database, including 552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (334 hom., cov: 33)
  • Exomes 𝑓: 0.0044 (218 hom.)
• Consequence: SOD1 ENST00000928717.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.586
• Publications: 15 publications found

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-DT (HGNC:55683): (SOD1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 21-31659661-A-G is Benign according to our data. Variant chr21-31659661-A-G is described in ClinVar as Benign. ClinVar VariationId is 339660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000928717.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD1-DT	NR_187558.1		n.364T>C		non_coding_transcript_exon	Exon 1 of 3
	SOD1	NM_000454.5	MANE Select	c.-109A>G		upstream_gene	N/A	NP_000445.1	P00441

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD1	ENST00000928717.1		c.-109A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000598776.1
	SOD1	ENST00000928718.1		c.-109A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000598777.1
	SOD1	ENST00000928720.1		c.-109A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000598779.1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5714 AN: 152174 Hom.: 331 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000661

Gnomad OTH AF: 0.0277

GnomAD4 exome AF: 0.00441 AC: 4545 AN: 1031450 Hom.: 218 Cov.: 13 AF XY: 0.00385 AC XY: 2036 AN XY: 528820

African (AFR) AF: 0.137 AC: 3421 AN: 24962

American (AMR) AF: 0.00813 AC: 324 AN: 39846

Ashkenazi Jewish (ASJ) AF: 0.000567 AC: 13 AN: 22916

East Asian (EAS) AF: 0.00 AC: 0 AN: 36020

South Asian (SAS) AF: 0.000200 AC: 15 AN: 75028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44840

Middle Eastern (MID) AF: 0.00683 AC: 34 AN: 4980

European-Non Finnish (NFE) AF: 0.000383 AC: 282 AN: 736510

Other (OTH) AF: 0.00984 AC: 456 AN: 46348

GnomAD4 genome AF: 0.0377 AC: 5736 AN: 152292 Hom.: 334 Cov.: 33 AF XY: 0.0359 AC XY: 2670 AN XY: 74472

African (AFR) AF: 0.130 AC: 5387 AN: 41548

American (AMR) AF: 0.0154 AC: 235 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000827 AC: 4 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000662 AC: 45 AN: 68026

Other (OTH) AF: 0.0274 AC: 58 AN: 2114

Alfa AF: 0.0273 Hom.: 136

Bravo AF: 0.0428

Asia WGS AF: 0.00953 AC: 34 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Amyotrophic lateral sclerosis type 1 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.71
PhyloP100		0.59
PromoterAI		-0.63	Under-expression
Mutation Taster		=292/8	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7277748; hg19: chr21-33031974; COSMIC: COSV54256003; COSMIC: COSV54256003;