chr21-27573957-A-G

Variant names:

• chr21-27573957-A-G
• rs1598848
• ENST00000773802.1:n.88-15961A>G

Variant summary

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

The ENST00000773802.1(ENSG00000300745):​n.88-15961A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 150,922 control chromosomes in the GnomAD database, including 25,225 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 0.57 (25225 hom., cov: 29)
• Consequence: ENSG00000300745 ENST00000773802.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 3 publications found

Genes affected

ENSG00000300745 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 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
ENSG00000300745	ENST00000773802.1	n.88-15961A>G		intron_variant	Intron 1 of 1
ENSG00000300745	ENST00000773803.1	n.446+3046A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86459 AN: 150810 Hom.: 25229 Cov.: 29

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.573 AC: 86476 AN: 150922 Hom.: 25225 Cov.: 29 AF XY: 0.584 AC XY: 43050 AN XY: 73708

African (AFR) AF: 0.469 AC: 19285 AN: 41116

American (AMR) AF: 0.624 AC: 9438 AN: 15132

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1974 AN: 3462

East Asian (EAS) AF: 0.572 AC: 2884 AN: 5040

South Asian (SAS) AF: 0.666 AC: 3188 AN: 4786

European-Finnish (FIN) AF: 0.725 AC: 7608 AN: 10494

Middle Eastern (MID) AF: 0.559 AC: 160 AN: 286

European-Non Finnish (NFE) AF: 0.593 AC: 40061 AN: 67608

Other (OTH) AF: 0.595 AC: 1245 AN: 2092

Alfa AF: 0.562 Hom.: 4231

Bravo AF: 0.557

Asia WGS AF: 0.627 AC: 2180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.37
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs1598848; hg19: chr21-28946276;