rs202446

Variant names:

• chr21-31656328-G-T
• rs202446
• ENST00000449339.1:n.399-901C>A

Variant summary

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

The ENST00000449339.1(SOD1-DT):​n.399-901C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 151,942 control chromosomes in the GnomAD database, including 993 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 0.10 (993 hom., cov: 31)
• Consequence: SOD1-DT ENST00000449339.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000449339.1. 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.791-901C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOD1-DT	ENST00000449339.1	TSL:3	n.399-901C>A		intron	N/A
	SOD1-DT	ENST00000752262.1		n.207-901C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15715 AN: 151822 Hom.: 992 Cov.: 31

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0149

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.103 AC: 15720 AN: 151942 Hom.: 993 Cov.: 31 AF XY: 0.100 AC XY: 7461 AN XY: 74260

African (AFR) AF: 0.0549 AC: 2272 AN: 41416

American (AMR) AF: 0.0986 AC: 1504 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3464

East Asian (EAS) AF: 0.0146 AC: 75 AN: 5152

South Asian (SAS) AF: 0.107 AC: 517 AN: 4814

European-Finnish (FIN) AF: 0.0917 AC: 968 AN: 10552

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9635 AN: 67976

Other (OTH) AF: 0.126 AC: 266 AN: 2108

Alfa AF: 0.125 Hom.: 177

Bravo AF: 0.100

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.63
PhyloP100		0.62

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs202446;

hg19: chr21-33028641;