rs2828099

Variant names:

• chr21-23380836-A-G
• rs2828099
• ENST00000262354.6:n.340+3852T>C

Variant summary

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

The ENST00000262354.6(ENSG00000228592):​n.340+3852T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,790 control chromosomes in the GnomAD database, including 10,917 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 0.37 (10917 hom., cov: 32)
• Consequence: ENSG00000228592 ENST00000262354.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 1 publications found

Genes affected

ENSG00000228592 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
D21S2088E	NR_040254.1	n.148+3852T>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000228592	ENST00000262354.6	n.340+3852T>C		intron_variant	Intron 1 of 4	1
ENSG00000228592	ENST00000653972.1	n.1353-7752T>C		intron_variant	Intron 2 of 5
ENSG00000228592	ENST00000654898.2	n.236+3852T>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56275 AN: 151672 Hom.: 10898 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.0756

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.371 AC: 56327 AN: 151790 Hom.: 10917 Cov.: 32 AF XY: 0.367 AC XY: 27221 AN XY: 74192

African (AFR) AF: 0.412 AC: 17052 AN: 41434

American (AMR) AF: 0.342 AC: 5215 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1157 AN: 3468

East Asian (EAS) AF: 0.0754 AC: 390 AN: 5174

South Asian (SAS) AF: 0.284 AC: 1369 AN: 4820

European-Finnish (FIN) AF: 0.353 AC: 3686 AN: 10446

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26453 AN: 67888

Other (OTH) AF: 0.373 AC: 788 AN: 2112

Alfa AF: 0.380 Hom.: 8982

Bravo AF: 0.372

Asia WGS AF: 0.212 AC: 735 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.91
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs2828099; hg19: chr21-24753158;