21-31646056-A-G

Variant names:

• chr21-31646056-A-G
• rs9974610
• ENST00000752262.1:n.360+9218T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000752262.1(SOD1-DT):​n.360+9218T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,176 control chromosomes in the GnomAD database, including 1,595 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1595 hom., cov: 32)
• Consequence: SOD1-DT ENST00000752262.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 9 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000752262.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD1-DT	ENST00000752262.1		n.360+9218T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19815 AN: 152058 Hom.: 1594 Cov.: 32

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.130 AC: 19821 AN: 152176 Hom.: 1595 Cov.: 32 AF XY: 0.128 AC XY: 9521 AN XY: 74374

African (AFR) AF: 0.0619 AC: 2570 AN: 41548

American (AMR) AF: 0.121 AC: 1841 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3472

East Asian (EAS) AF: 0.0147 AC: 76 AN: 5178

South Asian (SAS) AF: 0.109 AC: 526 AN: 4820

European-Finnish (FIN) AF: 0.146 AC: 1549 AN: 10576

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12382 AN: 67990

Other (OTH) AF: 0.146 AC: 309 AN: 2114

Alfa AF: 0.163 Hom.: 2776

Bravo AF: 0.122

Asia WGS AF: 0.0880 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.11
PhyloP100		-1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9974610; hg19: chr21-33018369;