rs9304221

Variant names:

• chr18-40422697-T-A
• rs9304221
• ENST00000723683.1:n.331+8608A>T

Variant summary

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

The ENST00000723683.1(ENSG00000294453):​n.331+8608A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,080 control chromosomes in the GnomAD database, including 4,472 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 0.22 (4472 hom., cov: 32)
• Consequence: ENSG00000294453 ENST00000723683.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538
• Publications: 3 publications found

Genes affected

ENSG00000294453 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 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
ENSG00000294453	ENST00000723683.1	n.331+8608A>T		intron_variant	Intron 1 of 2
ENSG00000294453	ENST00000723684.1	n.253+8608A>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33793 AN: 151962 Hom.: 4454 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.222 AC: 33836 AN: 152080 Hom.: 4472 Cov.: 32 AF XY: 0.230 AC XY: 17086 AN XY: 74330

African (AFR) AF: 0.205 AC: 8522 AN: 41508

American (AMR) AF: 0.330 AC: 5040 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 637 AN: 3472

East Asian (EAS) AF: 0.523 AC: 2691 AN: 5146

South Asian (SAS) AF: 0.484 AC: 2333 AN: 4816

European-Finnish (FIN) AF: 0.193 AC: 2047 AN: 10588

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11964 AN: 67962

Other (OTH) AF: 0.216 AC: 456 AN: 2114

Alfa AF: 0.210 Hom.: 467

Bravo AF: 0.228

Asia WGS AF: 0.520 AC: 1801 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.47
PhyloP100		-0.54

Splicing

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

Other links and lift over

dbSNP: rs9304221; hg19: chr18-38002661;