4-144559628-A-G

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000649263.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285713	ENST00000649263.1		n.328-143650T>C		intron	N/A	ENSP00000497507.1
	ENSG00000285783	ENST00000650526.1		n.223-143650T>C		intron	N/A

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 v4.9

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;