rs4131229

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ABCG5	NM_022436.3	c.501+841T>C		intron_variant		ENST00000405322.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG5	ENST00000405322.8	c.501+841T>C		intron_variant		1	NM_022436.3	P1
ABCG5	ENST00000486512.5	n.1153+841T>C		intron_variant, non_coding_transcript_variant		1
ABCG5	ENST00000409962.1	n.1268+841T>C		intron_variant, non_coding_transcript_variant		2
ABCG5	ENST00000644754.1	n.1155+841T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.368

Alfa AF: 0.391 Hom.: 6079

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs4131229; hg19: chr2-44058067;