chr11-119160042-T-C

Variant names:

• chr11-119160042-T-C
• rs674424
• NM_022169.5:c.1438-185T>C

Variant summary

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

The NM_022169.5(ABCG4):​c.1438-185T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 151,438 control chromosomes in the GnomAD database, including 49,299 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 0.80 (49299 hom., cov: 28)
• Consequence: ABCG4 NM_022169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 9 publications found

Genes affected

ABCG4 (HGNC:13884): (ATP binding cassette subfamily G member 4) The protein encoded by this gene is a member of the ATP-binding cassette (ABC) transporter superfamily. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). The encoded protein is a member of the White subfamily and plays an important role in cellular cholesterol homeostasis. This protein functions as either a homodimer or as a heterodimer with another ABC subfamily protein such as ABCG1. [provided by RefSeq, Jan 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG4	NM_022169.5	c.1438-185T>C		intron_variant	Intron 12 of 14	ENST00000619701.5	NP_071452.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG4	ENST00000619701.5	c.1438-185T>C		intron_variant	Intron 12 of 14	1	NM_022169.5	ENSP00000481728.1
ABCG4	ENST00000622721.1	c.1438-185T>C		intron_variant	Intron 11 of 13	1		ENSP00000484289.1
ABCG4	ENST00000533694.5	n.2575-185T>C		intron_variant	Intron 9 of 9	1
ABCG4	ENST00000615496.4	c.1438-185T>C		intron_variant	Intron 12 of 14	2		ENSP00000479253.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 120564 AN: 151320 Hom.: 49252 Cov.: 28

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.797 AC: 120661 AN: 151438 Hom.: 49299 Cov.: 28 AF XY: 0.799 AC XY: 59099 AN XY: 73920

African (AFR) AF: 0.948 AC: 39112 AN: 41276

American (AMR) AF: 0.589 AC: 8934 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2853 AN: 3472

East Asian (EAS) AF: 0.937 AC: 4779 AN: 5102

South Asian (SAS) AF: 0.858 AC: 4096 AN: 4776

European-Finnish (FIN) AF: 0.804 AC: 8428 AN: 10486

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 49930 AN: 67838

Other (OTH) AF: 0.785 AC: 1651 AN: 2104

Alfa AF: 0.754 Hom.: 145392

Bravo AF: 0.785

Asia WGS AF: 0.883 AC: 3073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.26
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs674424; hg19: chr11-119030752;