rs915841

Variant names:

• chr21-42259328-T-C
• rs915841
• ENST00000398437.1:c.399T>C

Your query was ambiguous. Multiple possible variants found:

• chr21-42259328-T-C
• chr21-42259328-T-G

Variant summary

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

The ENST00000398437.1(ABCG1):​c.399T>C​(p.His133His) 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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ABCG1	NM_016818.3	c.287-11742T>C		intron_variant	Intron 2 of 14	ENST00000398449.8	NP_058198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG1	ENST00000398437.1	c.399T>C	p.His133His	synonymous_variant	Exon 2 of 16	1		ENSP00000381464.1
ABCG1	ENST00000398449.8	c.287-11742T>C		intron_variant	Intron 2 of 14	1	NM_016818.3	ENSP00000381467.3

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

GnomAD2 exomes AF: 0.151 AC: 22256 AN: 147144 AF XY: 0.148

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 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

African (AFR) AF: 0.393 AC: 12342 AN: 31418

American (AMR) AF: 0.162 AC: 5711 AN: 35350

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 2877 AN: 24996

East Asian (EAS) AF: 0.109 AC: 3874 AN: 35660

South Asian (SAS) AF: 0.129 AC: 10127 AN: 78694

European-Finnish (FIN) AF: 0.145 AC: 6971 AN: 48090

Middle Eastern (MID) AF: 0.0956 AC: 517 AN: 5406

European-Non Finnish (NFE) AF: 0.162 AC: 174897 AN: 1077268

Other (OTH) AF: 0.163 AC: 9455 AN: 57854

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

African (AFR) AF: 0.385 AC: 15968 AN: 41508

American (AMR) AF: 0.160 AC: 2441 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3470

East Asian (EAS) AF: 0.102 AC: 526 AN: 5182

South Asian (SAS) AF: 0.125 AC: 602 AN: 4828

European-Finnish (FIN) AF: 0.142 AC: 1505 AN: 10596

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10457 AN: 67990

Other (OTH) AF: 0.169 AC: 358 AN: 2114

Alfa AF: 0.172 Hom.: 2163

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
PhyloP100		-1.0
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: rs915841; hg19: chr21-43679438; COSMIC: COSV59206265;