21-42219222-CCCGCCGCCGCCGCCGCCGCCG-CCCGCCGCCGCCG

Variant names:

• chr21-42219222-CCCGCCGCCG-C
• rs2234716
• NM_016818.3:c.-17_-9delGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016818.3(ABCG1):​c.-17_-9delGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000376 in 1,470,270 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00037 (1 hom.)
• Consequence: ABCG1 NM_016818.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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]

LOC105372814 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG1	NM_016818.3	c.-17_-9delGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 15	ENST00000398449.8	NP_058198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG1	ENST00000398449	c.-17_-9delGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 15	1	NM_016818.3	ENSP00000381467.3

Frequencies

GnomAD3 genomes AF: 0.000439 AC: 66 AN: 150178 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000317

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00172

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000386

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000932 AC: 71 AN: 76150 Hom.: 0 AF XY: 0.000820 AC XY: 35 AN XY: 42682

Gnomad AFR exome AF: 0.00201

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.000410

Gnomad EAS exome AF: 0.00118

Gnomad SAS exome AF: 0.000660

Gnomad FIN exome AF: 0.000404

Gnomad NFE exome AF: 0.000729

Gnomad OTH exome AF: 0.00146

GnomAD4 exome AF: 0.000368 AC: 486 AN: 1319988 Hom.: 1 AF XY: 0.000385 AC XY: 251 AN XY: 651838

Gnomad4 AFR exome AF: 0.000700

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.000352

Gnomad4 EAS exome AF: 0.000784

Gnomad4 SAS exome AF: 0.000683

Gnomad4 FIN exome AF: 0.000327

Gnomad4 NFE exome AF: 0.000308

Gnomad4 OTH exome AF: 0.000238

GnomAD4 genome AF: 0.000446 AC: 67 AN: 150282 Hom.: 0 Cov.: 26 AF XY: 0.000436 AC XY: 32 AN XY: 73404

Gnomad4 AFR AF: 0.000341

Gnomad4 AMR AF: 0.00172

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000386

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2234716; hg19: chr21-43639332;