rs4821469

Variant names:

• chr22-36220399-T-C
• rs4821469
• ENST00000691931.3:n.-136T>C

Variant summary

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

The ENST00000691931.3(ENSG00000288778):​n.-136T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,022 control chromosomes in the GnomAD database, including 6,242 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 (6242 hom., cov: 31)
• Consequence: ENSG00000288778 ENST00000691931.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 20 publications found

Genes affected

ENSG00000288778 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 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
ENSG00000288778	ENST00000691931.3	n.-136T>C		upstream_gene_variant
ENSG00000288778	ENST00000737366.1	n.-139T>C		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31424 AN: 151904 Hom.: 6233 Cov.: 31

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0972

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0591

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0768

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0829

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.207 AC: 31473 AN: 152022 Hom.: 6242 Cov.: 31 AF XY: 0.203 AC XY: 15111 AN XY: 74310

African (AFR) AF: 0.524 AC: 21674 AN: 41368

American (AMR) AF: 0.0970 AC: 1483 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3470

East Asian (EAS) AF: 0.0588 AC: 305 AN: 5186

South Asian (SAS) AF: 0.154 AC: 740 AN: 4816

European-Finnish (FIN) AF: 0.0768 AC: 814 AN: 10602

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0829 AC: 5638 AN: 67972

Other (OTH) AF: 0.163 AC: 343 AN: 2108

Alfa AF: 0.119 Hom.: 7168

Bravo AF: 0.223

Asia WGS AF: 0.132 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.69
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs4821469; hg19: chr22-36616445;