chr21-25214010-A-G

Variant names:

• chr21-25214010-A-G
• rs2829644
• ENST00000409758.1:n.90-38565T>C

Variant summary

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

The ENST00000409758.1(ENSG00000222042):​n.90-38565T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 152,132 control chromosomes in the GnomAD database, including 308 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 0.059 (308 hom., cov: 32)
• Consequence: ENSG00000222042 ENST00000409758.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 7 publications found

Genes affected

ENSG00000222042 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 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
ENSG00000222042	ENST00000409758.1	n.90-38565T>C		intron_variant	Intron 1 of 3	3
ENSG00000222042	ENST00000656005.1	n.218-38565T>C		intron_variant	Intron 2 of 4
ENSG00000222042	ENST00000667825.2	n.314-38565T>C		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.0589 AC: 8955 AN: 152014 Hom.: 309 Cov.: 32

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0376

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0479

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0619

Gnomad OTH AF: 0.0574

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

GnomAD4 genome AF: 0.0589 AC: 8953 AN: 152132 Hom.: 308 Cov.: 32 AF XY: 0.0598 AC XY: 4450 AN XY: 74368

African (AFR) AF: 0.0422 AC: 1754 AN: 41516

American (AMR) AF: 0.0376 AC: 574 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3470

East Asian (EAS) AF: 0.136 AC: 702 AN: 5160

South Asian (SAS) AF: 0.162 AC: 780 AN: 4808

European-Finnish (FIN) AF: 0.0479 AC: 508 AN: 10598

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0619 AC: 4207 AN: 67994

Other (OTH) AF: 0.0596 AC: 126 AN: 2114

Alfa AF: 0.0606 Hom.: 592

Bravo AF: 0.0545

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.43
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs2829644; hg19: chr21-26586324;