rs449725

Variant names:

• chr2-202993-C-G
• rs449725
• ENST00000653001.1:n.194+2763C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000665534.1(ENSG00000227061):​n.408+5C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,036 control chromosomes in the GnomAD database, including 60,383 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 0.89 (60383 hom., cov: 31)
• Consequence: ENSG00000227061 ENST00000665534.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744

Genes affected

ENSG00000227061 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 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
ENSG00000227061	ENST00000653001.1	n.194+2763C>G		intron_variant	Intron 2 of 2
ENSG00000227061	ENST00000665534.1	n.408+5C>G		splice_region_variant, intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135292 AN: 151920 Hom.: 60336 Cov.: 31

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.821

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.904

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.889

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

GnomAD4 genome AF: 0.891 AC: 135393 AN: 152036 Hom.: 60383 Cov.: 31 AF XY: 0.889 AC XY: 66061 AN XY: 74286

Gnomad4 AFR AF: 0.933

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.884

Gnomad4 EAS AF: 0.878

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.837

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.888

Alfa AF: 0.890 Hom.: 7468

Bravo AF: 0.896

Asia WGS AF: 0.898 AC: 3123 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	0.59
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs449725; hg19: chr2-202993;