rs4522221

Variant names:

• chr12-17110968-C-T
• rs4522221
• ENST00000649143.1:n.901+18024G>A

Variant summary

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

The ENST00000649143.1(ENSG00000285724):​n.901+18024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,950 control chromosomes in the GnomAD database, including 22,071 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 0.53 (22071 hom., cov: 33)
• Consequence: ENSG00000285724 ENST00000649143.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 2 publications found

Genes affected

ENSG00000285724 (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 (EAS) allele frequency at 95% confidence interval = 0.735 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
ENSG00000285724	ENST00000649143.1	n.901+18024G>A		intron_variant	Intron 6 of 6
ENSG00000285724	ENST00000671686.1	n.507+18024G>A		intron_variant	Intron 4 of 4
ENSG00000287455	ENST00000792895.1	n.216-33215C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81124 AN: 151832 Hom.: 22054 Cov.: 33

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.534 AC: 81176 AN: 151950 Hom.: 22071 Cov.: 33 AF XY: 0.539 AC XY: 40078 AN XY: 74300

African (AFR) AF: 0.508 AC: 21047 AN: 41418

American (AMR) AF: 0.585 AC: 8935 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1900 AN: 3468

East Asian (EAS) AF: 0.754 AC: 3900 AN: 5170

South Asian (SAS) AF: 0.691 AC: 3337 AN: 4826

European-Finnish (FIN) AF: 0.566 AC: 5972 AN: 10542

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34429 AN: 67934

Other (OTH) AF: 0.534 AC: 1126 AN: 2110

Alfa AF: 0.513 Hom.: 2592

Bravo AF: 0.533

Asia WGS AF: 0.727 AC: 2521 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.28
DANN	Benign	0.45
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs4522221; hg19: chr12-17263902;