rs4295666

Variant names:

• chr8-22704579-A-C
• rs4295666
• ENST00000523627.1:n.164+14266A>C

Variant summary

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

The ENST00000523627.1(ENSG00000253125):​n.164+14266A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,008 control chromosomes in the GnomAD database, including 4,245 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 0.23 (4245 hom., cov: 32)
• Consequence: ENSG00000253125 ENST00000523627.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.870
• Publications: 4 publications found

Genes affected

ENSG00000253125 (HGNC:58186):

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 = 0.257 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
ENSG00000253125	ENST00000523627.1	n.164+14266A>C		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34356 AN: 151890 Hom.: 4236 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.226 AC: 34375 AN: 152008 Hom.: 4245 Cov.: 32 AF XY: 0.222 AC XY: 16482 AN XY: 74314

African (AFR) AF: 0.186 AC: 7713 AN: 41416

American (AMR) AF: 0.244 AC: 3726 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1434 AN: 3470

East Asian (EAS) AF: 0.0102 AC: 53 AN: 5180

South Asian (SAS) AF: 0.195 AC: 939 AN: 4824

European-Finnish (FIN) AF: 0.187 AC: 1973 AN: 10550

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17663 AN: 67980

Other (OTH) AF: 0.247 AC: 521 AN: 2112

Alfa AF: 0.252 Hom.: 15814

Bravo AF: 0.226

Asia WGS AF: 0.0950 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.47
DANN	Benign	0.30
PhyloP100		-0.87

Splicing

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

Other links and lift over

dbSNP: rs4295666; hg19: chr8-22562092;