rs1828591

Variant names:

• chr4-144559628-A-G
• rs1828591
• ENST00000649263.1:n.328-143650T>C

Variant summary

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

The ENST00000649263.1(ENSG00000285713):​n.328-143650T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,006 control chromosomes in the GnomAD database, including 14,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.43 (14210 hom., cov: 32)
• Consequence: ENSG00000285713 ENST00000649263.1 intron
• Clinical Significance: association no assertion criteria provided O:2
• Conservation: PhyloP100: -0.420
• Publications: 59 publications found

Genes affected

ENSG00000285713 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105377462	XR_939272.3	n.164+2356T>C		intron_variant	Intron 1 of 7
LOC105377462	XR_939273.3	n.164+2356T>C		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285713	ENST00000649263.1	n.328-143650T>C		intron_variant	Intron 4 of 8			ENSP00000497507.1
ENSG00000285783	ENST00000650526.1	n.223-143650T>C		intron_variant	Intron 2 of 14

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64965 AN: 151888 Hom.: 14197 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.428 AC: 65008 AN: 152006 Hom.: 14210 Cov.: 32 AF XY: 0.432 AC XY: 32078 AN XY: 74296

African (AFR) AF: 0.471 AC: 19529 AN: 41450

American (AMR) AF: 0.342 AC: 5219 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1263 AN: 3472

East Asian (EAS) AF: 0.299 AC: 1551 AN: 5180

South Asian (SAS) AF: 0.493 AC: 2377 AN: 4822

European-Finnish (FIN) AF: 0.537 AC: 5664 AN: 10538

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28130 AN: 67960

Other (OTH) AF: 0.379 AC: 800 AN: 2110

Alfa AF: 0.415 Hom.: 32590

Bravo AF: 0.408

Asia WGS AF: 0.382 AC: 1331 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:2

Revision: no assertion criteria provided

Submissions by phenotype

Chronic obstructive pulmonary disease, biomass related Other:1

Feb 12, 2020

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

- -

Chronic obstructive pulmonary disease Other:1

Dec 08, 2019

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.57
PhyloP100		-0.42

Splicing

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

Other links and lift over

dbSNP: rs1828591; hg19: chr4-145480780;