21-42219222-CCCGCCGCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCG

Variant names:

• chr21-42219222-CCCGCCG-C
• rs2234716
• NM_016818.3:c.-14_-9delGCCGCC

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_016818.3(ABCG1):​c.-14_-9delGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,472,354 control chromosomes in the GnomAD database, including 12,832 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.14 (1595 hom., cov: 26)
  • Exomes 𝑓: 0.14 (11237 hom.)
• Consequence: ABCG1 NM_016818.3 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.18

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 Benign. Variant got -9 ACMG points.

• BP6: Variant 21-42219222-CCCGCCG-C is Benign according to our data. Variant chr21-42219222-CCCGCCG-C is described in ClinVar as [Benign]. Clinvar id is 3059244.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG1	NM_016818.3	c.-14_-9delGCCGCC		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.-14_-9delGCCGCC		5_prime_UTR_variant	Exon 1 of 15	1	NM_016818.3	ENSP00000381467.3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20669 AN: 150124 Hom.: 1596 Cov.: 26

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.170

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.132

GnomAD3 exomes AF: 0.233 AC: 17772 AN: 76150 Hom.: 1414 AF XY: 0.229 AC XY: 9780 AN XY: 42682

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.249

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.338

Gnomad SAS exome AF: 0.233

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.139 AC: 183928 AN: 1322126 Hom.: 11237 AF XY: 0.141 AC XY: 91765 AN XY: 653006

Gnomad4 AFR exome AF: 0.0816

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.210

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.138 AC: 20664 AN: 150228 Hom.: 1595 Cov.: 26 AF XY: 0.143 AC XY: 10461 AN XY: 73368

Gnomad4 AFR AF: 0.0776

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.130

Bravo AF: 0.135

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ABCG1-related disorder Benign:1

May 24, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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;