22-23893173-A-G

Variant names:

• chr22-23893173-A-G
• rs4822446
• ENST00000433835.3:c.432-1599A>G

Variant summary

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

The ENST00000433835.3(ENSG00000251357):​c.432-1599A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,136 control chromosomes in the GnomAD database, including 3,139 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 0.20 (3139 hom., cov: 32)
• Consequence: ENSG00000251357 ENST00000433835.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297
• Publications: 4 publications found

Genes affected

ENSG00000251357 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 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
ENSG00000251357	ENST00000433835.3	c.432-1599A>G		intron_variant	Intron 4 of 5	5		ENSP00000400325.3
ENSG00000290199	ENST00000717616.1	n.213-1707T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30032 AN: 152018 Hom.: 3130 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.198 AC: 30071 AN: 152136 Hom.: 3139 Cov.: 32 AF XY: 0.202 AC XY: 15051 AN XY: 74362

African (AFR) AF: 0.224 AC: 9299 AN: 41486

American (AMR) AF: 0.235 AC: 3598 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 457 AN: 3468

East Asian (EAS) AF: 0.186 AC: 963 AN: 5178

South Asian (SAS) AF: 0.233 AC: 1126 AN: 4828

European-Finnish (FIN) AF: 0.228 AC: 2410 AN: 10592

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11617 AN: 67984

Other (OTH) AF: 0.178 AC: 377 AN: 2114

Alfa AF: 0.162 Hom.: 826

Bravo AF: 0.197

Asia WGS AF: 0.231 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.27
PhyloP100		-0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4822446; hg19: chr22-24235360;