rs4461358

Variant names:

• chr22-23917919-T-C
• rs4461358
• ENST00000703580.1:n.386+8525A>G

Variant summary

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

The ENST00000703580.1(ENSG00000290199):​n.386+8525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 151,844 control chromosomes in the GnomAD database, including 5,669 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 0.27 (5669 hom., cov: 30)
• Consequence: ENSG00000290199 ENST00000703580.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.980
• Publications: 9 publications found

Genes affected

ENSG00000290199 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 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
ENSG00000290199	ENST00000703580.1	n.386+8525A>G		intron_variant	Intron 3 of 3
ENSG00000290199	ENST00000717616.1	n.212+8525A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41227 AN: 151726 Hom.: 5650 Cov.: 30

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.272 AC: 41281 AN: 151844 Hom.: 5669 Cov.: 30 AF XY: 0.268 AC XY: 19882 AN XY: 74238

African (AFR) AF: 0.307 AC: 12687 AN: 41340

American (AMR) AF: 0.226 AC: 3443 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3472

East Asian (EAS) AF: 0.413 AC: 2134 AN: 5168

South Asian (SAS) AF: 0.248 AC: 1193 AN: 4820

European-Finnish (FIN) AF: 0.216 AC: 2282 AN: 10556

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17877 AN: 67918

Other (OTH) AF: 0.280 AC: 589 AN: 2106

Alfa AF: 0.266 Hom.: 704

Bravo AF: 0.275

Asia WGS AF: 0.329 AC: 1142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.85
PhyloP100		-0.98

Splicing

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

Other links and lift over

dbSNP: rs4461358; hg19: chr22-24260106;