rs4131229

Variant names:

• chr2-43830928-A-G
• rs4131229
• NM_022436.3:c.501+841T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-43830928-A-G
• chr2-43830928-A-T

Variant summary

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

The NM_022436.3(ABCG5):​c.501+841T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,150 control chromosomes in the GnomAD database, including 11,008 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 0.36 (11008 hom., cov: 32)
• Consequence: ABCG5 NM_022436.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 11 publications found

Genes affected

ABCG5 (HGNC:13886): (ATP binding cassette subfamily G member 5) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. 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). This protein is a member of the White subfamily. The protein encoded by this gene functions as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG8. Mutations in this gene may contribute to sterol accumulation and atheroschlerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]

ABCG5 Gene-Disease associations (from GenCC):

• sitosterolemia

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• sitosterolemia 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• sitosterolemia 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

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 (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG5	NM_022436.3	c.501+841T>C		intron_variant	Intron 4 of 12	ENST00000405322.8	NP_071881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG5	ENST00000405322.8	c.501+841T>C		intron_variant	Intron 4 of 12	1	NM_022436.3	ENSP00000384513.2
ABCG5	ENST00000486512.5	n.1153+841T>C		intron_variant	Intron 3 of 8	1
ABCG5	ENST00000409962.1	n.1268+841T>C		intron_variant	Intron 3 of 8	2
ABCG5	ENST00000644754.1	n.1155+841T>C		intron_variant	Intron 3 of 9

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54378 AN: 152032 Hom.: 10996 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.357 AC: 54393 AN: 152150 Hom.: 11008 Cov.: 32 AF XY: 0.365 AC XY: 27135 AN XY: 74394

African (AFR) AF: 0.197 AC: 8180 AN: 41518

American (AMR) AF: 0.378 AC: 5784 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3470

East Asian (EAS) AF: 0.825 AC: 4263 AN: 5166

South Asian (SAS) AF: 0.601 AC: 2894 AN: 4816

European-Finnish (FIN) AF: 0.395 AC: 4176 AN: 10582

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26858 AN: 67994

Other (OTH) AF: 0.368 AC: 777 AN: 2114

Alfa AF: 0.389 Hom.: 6679

Bravo AF: 0.345

Asia WGS AF: 0.625 AC: 2173 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	8.8
DANN	Benign	0.81
PhyloP100		-0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs4131229; hg19: chr2-44058067;