21-42219222-C-CCCG

Variant names:

• chr21-42219222-C-CCCG
• rs2234716
• NM_016818.3:c.-11_-9dupGCC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_016818.3(ABCG1):​c.-11_-9dupGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,472,956 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0045 (5 hom., cov: 26)
  • Exomes 𝑓: 0.0013 (3 hom.)
• Consequence: ABCG1 NM_016818.3 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0270

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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 21-42219222-C-CCCG is Benign according to our data. Variant chr21-42219222-C-CCCG is described in ClinVar as [Benign]. Clinvar id is 3041521.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG1	NM_016818.3	c.-11_-9dupGCC		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.-11_-9dupGCC		5_prime_UTR_variant	Exon 1 of 15	1	NM_016818.3	ENSP00000381467.3

Frequencies

GnomAD3 genomes AF: 0.00450 AC: 676 AN: 150178 Hom.: 5 Cov.: 26

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00132

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00157

Gnomad SAS AF: 0.00294

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.00108

Gnomad OTH AF: 0.00341

GnomAD3 exomes AF: 0.00207 AC: 158 AN: 76150 Hom.: 1 AF XY: 0.00201 AC XY: 86 AN XY: 42682

Gnomad AFR exome AF: 0.0109

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00103

Gnomad EAS exome AF: 0.000708

Gnomad SAS exome AF: 0.00264

Gnomad FIN exome AF: 0.000202

Gnomad NFE exome AF: 0.00172

Gnomad OTH exome AF: 0.00243

GnomAD4 exome AF: 0.00133 AC: 1765 AN: 1322674 Hom.: 3 Cov.: 20 AF XY: 0.00133 AC XY: 866 AN XY: 653220

Gnomad4 AFR exome AF: 0.0138

Gnomad4 AMR exome AF: 0.00162

Gnomad4 ASJ exome AF: 0.000701

Gnomad4 EAS exome AF: 0.000617

Gnomad4 SAS exome AF: 0.00182

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.000980

Gnomad4 OTH exome AF: 0.00216

GnomAD4 genome AF: 0.00449 AC: 675 AN: 150282 Hom.: 5 Cov.: 26 AF XY: 0.00430 AC XY: 316 AN XY: 73406

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.00139

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.00157

Gnomad4 SAS AF: 0.00294

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00108

Gnomad4 OTH AF: 0.00337

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ABCG1-related disorder Benign:1

May 22, 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;