21-33902813-G-T

Variant names:

• chr21-33902813-G-T
• rs731059
• ENST00000429238.2:c.441+4528C>A

Variant summary

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

The ENST00000429238.2(ENSG00000249209):​c.441+4528C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,084 control chromosomes in the GnomAD database, including 7,843 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 0.32 (7843 hom., cov: 32)
• Consequence: ENSG00000249209 ENST00000429238.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 6 publications found

Genes affected

ENSG00000249209 (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 = 0.379 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429238.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000249209	ENST00000429238.2	TSL:5	c.441+4528C>A		intron	N/A	ENSP00000394107.2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48612 AN: 151964 Hom.: 7841 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.320 AC: 48636 AN: 152084 Hom.: 7843 Cov.: 32 AF XY: 0.320 AC XY: 23782 AN XY: 74332

African (AFR) AF: 0.384 AC: 15938 AN: 41488

American (AMR) AF: 0.271 AC: 4142 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 890 AN: 3466

East Asian (EAS) AF: 0.343 AC: 1773 AN: 5164

South Asian (SAS) AF: 0.297 AC: 1435 AN: 4826

European-Finnish (FIN) AF: 0.321 AC: 3393 AN: 10580

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20041 AN: 67966

Other (OTH) AF: 0.287 AC: 607 AN: 2112

Alfa AF: 0.301 Hom.: 20148

Bravo AF: 0.318

Asia WGS AF: 0.330 AC: 1147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.22
DANN	Benign	0.85
PhyloP100		-1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs731059; hg19: chr21-35275117;