rs4953023

chr2-43846861-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022437.3(ABCG8):c.322+550G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 187,758 control chromosomes in the GnomAD database, including 498 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 0.068 (421 hom., cov: 32)
  • Exomes 𝑓: 0.063 (77 hom.)
• Consequence: ABCG8 NM_022437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

Genes affected

ABCG8 (HGNC:13887): (ATP binding cassette subfamily G member 8) 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 to exclude non-cholesterol sterol entry at the intestinal level, promote excretion of cholesterol and sterols into bile, and to facilitate transport of sterols back into the intestinal lumen. It is expressed in a tissue-specific manner in the liver, intestine, and gallbladder. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG5. Mutations in this gene may contribute to sterol accumulation and atherosclerosis, 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG8	NM_022437.3	c.322+550G>A		intron_variant		ENST00000272286.4
ABCG8	NM_001357321.2	c.322+550G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG8	ENST00000272286.4	c.322+550G>A		intron_variant		1	NM_022437.3	P1
ABCG8	ENST00000644611.1	c.334+550G>A		intron_variant
ABCG8	ENST00000643284.1	n.1329G>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10413 AN: 152052 Hom.: 421 Cov.: 32

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0715

Gnomad ASJ AF: 0.0999

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.0355

Gnomad FIN AF: 0.0874

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0619

Gnomad OTH AF: 0.0608

GnomAD4 exome AF: 0.0633 AC: 2252 AN: 35588 Hom.: 77 Cov.: 0 AF XY: 0.0615 AC XY: 1109 AN XY: 18030

Gnomad4 AFR exome AF: 0.0782

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.0866

Gnomad4 EAS exome AF: 0.0109

Gnomad4 SAS exome AF: 0.0341

Gnomad4 FIN exome AF: 0.0853

Gnomad4 NFE exome AF: 0.0652

Gnomad4 OTH exome AF: 0.0637

GnomAD4 genome AF: 0.0685 AC: 10423 AN: 152170 Hom.: 421 Cov.: 32 AF XY: 0.0680 AC XY: 5061 AN XY: 74392

Gnomad4 AFR AF: 0.0821

Gnomad4 AMR AF: 0.0716

Gnomad4 ASJ AF: 0.0999

Gnomad4 EAS AF: 0.0154

Gnomad4 SAS AF: 0.0355

Gnomad4 FIN AF: 0.0874

Gnomad4 NFE AF: 0.0619

Gnomad4 OTH AF: 0.0602

Alfa AF: 0.0633 Hom.: 625

Bravo AF: 0.0715

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.6
Dann	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs4953023; hg19: chr2-44074000;