rs543874

Variant names:

• chr1-177920345-A-G
• rs543874
• ENST00000664407.1:n.-193T>C

Variant summary

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

The ENST00000664407.1(ENSG00000227579):​n.-193T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,134 control chromosomes in the GnomAD database, including 3,365 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 0.21 (3365 hom., cov: 32)
• Consequence: ENSG00000227579 ENST00000664407.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32
• Publications: 238 publications found

Genes affected

ENSG00000227579 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000227579	ENST00000664407.1	n.-193T>C		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31173 AN: 152018 Hom.: 3364 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.205 AC: 31188 AN: 152134 Hom.: 3365 Cov.: 32 AF XY: 0.204 AC XY: 15164 AN XY: 74368

African (AFR) AF: 0.256 AC: 10627 AN: 41456

American (AMR) AF: 0.206 AC: 3149 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3472

East Asian (EAS) AF: 0.172 AC: 888 AN: 5172

South Asian (SAS) AF: 0.147 AC: 709 AN: 4828

European-Finnish (FIN) AF: 0.167 AC: 1772 AN: 10582

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13020 AN: 68008

Other (OTH) AF: 0.191 AC: 405 AN: 2116

Alfa AF: 0.194 Hom.: 13035

Bravo AF: 0.211

Asia WGS AF: 0.144 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Benign	0.56
PhyloP100		2.3

Splicing

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

Other links and lift over

dbSNP: rs543874; hg19: chr1-177889480;