ENST00000582441.1:c.438+2421C>T

Variant names:

• chr17-27801702-G-A
• rs9282799
• ENST00000582441.1:c.438+2421C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The ENST00000582441.1(ENSG00000266202):​c.438+2421C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 152,210 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as protective (no stars).

• Frequency: Genomes: 𝑓 0.014 (47 hom., cov: 32)
• Consequence: ENSG00000266202 ENST00000582441.1 intron
• Clinical Significance: protective no assertion criteria provided B:1
• Conservation: PhyloP100: -0.372
• Publications: 31 publications found

Genes affected

ENSG00000266202 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0137 (2092/152210) while in subpopulation AFR AF = 0.0463 (1921/41532). AF 95% confidence interval is 0.0445. There are 47 homozygotes in GnomAd4. There are 1039 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 47 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000582441.1. 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
	ENSG00000266202	ENST00000582441.1	TSL:4	c.438+2421C>T		intron	N/A	ENSP00000462879.1	J3KTA2

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2087 AN: 152092 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00642

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0115

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

GnomAD4 genome AF: 0.0137 AC: 2092 AN: 152210 Hom.: 47 Cov.: 32 AF XY: 0.0140 AC XY: 1039 AN XY: 74430

African (AFR) AF: 0.0463 AC: 1921 AN: 41532

American (AMR) AF: 0.00641 AC: 98 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 67998

Other (OTH) AF: 0.0114 AC: 24 AN: 2108

Alfa AF: 0.0164 Hom.: 4

Bravo AF: 0.0153

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: protective

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Malaria, resistance to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.82
DANN	Benign	0.41
PhyloP100		-0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9282799; hg19: chr17-26128728;