rs915841

Positions:

• chr21-42259328-T-C

Variant summary

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

The ENST00000398437.1(ABCG1):​c.399T>C​(p.His133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,546,928 control chromosomes in the GnomAD database, including 24,163 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 0.21 (4319 hom., cov: 33)
  • Exomes 𝑓: 0.16 (19844 hom.)
• Consequence: ABCG1 ENST00000398437.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

ABCG1 (HGNC:73): (ATP binding cassette subfamily G member 1) 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. It is involved in macrophage cholesterol and phospholipids transport, and may regulate cellular lipid homeostasis in other cell types. Six alternative splice variants have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCG1	NM_016818.3	c.287-11742T>C		intron_variant		ENST00000398449.8	NP_058198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG1	ENST00000398449.8	c.287-11742T>C		intron_variant		1	NM_016818.3	ENSP00000381467	P1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32378 AN: 152074 Hom.: 4304 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.173

GnomAD3 exomes AF: 0.151 AC: 22256 AN: 147144 Hom.: 2025 AF XY: 0.148 AC XY: 11736 AN XY: 79144

Gnomad AFR exome AF: 0.389

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.0933

Gnomad SAS exome AF: 0.125

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.163 AC: 226771 AN: 1394736 Hom.: 19844 Cov.: 32 AF XY: 0.160 AC XY: 110113 AN XY: 687768

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.213 AC: 32438 AN: 152192 Hom.: 4319 Cov.: 33 AF XY: 0.209 AC XY: 15566 AN XY: 74402

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.169

Alfa AF: 0.171 Hom.: 1998

Bravo AF: 0.223

Asia WGS AF: 0.141 AC: 495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.16
DANN	Benign	0.37

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: rs915841; hg19: chr21-43679438; COSMIC: COSV59206265;