rs449725

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

Genes affected

ENSG00000227061 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000665534.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000227061	ENST00000653001.1		n.194+2763C>G		intron	N/A
	ENSG00000227061	ENST00000665534.1		n.408+5C>G		splice_region intron	N/A
	ENSG00000297863	ENST00000751437.1		n.134-865G>C		intron	N/A

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

African (AFR) AF: 0.933 AC: 38703 AN: 41480

American (AMR) AF: 0.882 AC: 13461 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3066 AN: 3470

East Asian (EAS) AF: 0.878 AC: 4525 AN: 5156

South Asian (SAS) AF: 0.914 AC: 4382 AN: 4794

European-Finnish (FIN) AF: 0.837 AC: 8829 AN: 10550

Middle Eastern (MID) AF: 0.904 AC: 264 AN: 292

European-Non Finnish (NFE) AF: 0.876 AC: 59542 AN: 68004

Other (OTH) AF: 0.888 AC: 1872 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.59
DANN	Benign	0.70
PhyloP100		-0.74

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs449725;

hg19: chr2-202993;