21-42219222-CCCGCCGCCGCCG-C

Variant names:

• chr21-42219222-CCCGCCGCCGCCG-C
• rs2234716
• NM_016818.3:c.-20_-9delGCCGCCGCCGCC

Variant summary

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

The NM_016818.3(ABCG1):​c.-20_-9delGCCGCCGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,474,122 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0020 (13 hom.)
• Consequence: ABCG1 NM_016818.3 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• 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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 21-42219222-CCCGCCGCCGCCG-C is Benign according to our data. Variant chr21-42219222-CCCGCCGCCGCCG-C is described in ClinVar as [Benign]. Clinvar id is 3053710.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG1	NM_016818.3	c.-20_-9delGCCGCCGCCGCC		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.-20_-9delGCCGCCGCCGCC		5_prime_UTR_variant	Exon 1 of 15	1	NM_016818.3	ENSP00000381467.3

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 257 AN: 150180 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000708

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00371

Gnomad ASJ AF: 0.0102

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00180

Gnomad OTH AF: 0.00243

GnomAD3 exomes AF: 0.00457 AC: 348 AN: 76150 Hom.: 7 AF XY: 0.00403 AC XY: 172 AN XY: 42682

Gnomad AFR exome AF: 0.000403

Gnomad AMR exome AF: 0.00876

Gnomad ASJ exome AF: 0.0172

Gnomad EAS exome AF: 0.000472

Gnomad SAS exome AF: 0.000440

Gnomad FIN exome AF: 0.00101

Gnomad NFE exome AF: 0.00391

Gnomad OTH exome AF: 0.00584

GnomAD4 exome AF: 0.00204 AC: 2698 AN: 1323838 Hom.: 13 AF XY: 0.00199 AC XY: 1301 AN XY: 653840

Gnomad4 AFR exome AF: 0.000441

Gnomad4 AMR exome AF: 0.00652

Gnomad4 ASJ exome AF: 0.0122

Gnomad4 EAS exome AF: 0.0000325

Gnomad4 SAS exome AF: 0.000493

Gnomad4 FIN exome AF: 0.00141

Gnomad4 NFE exome AF: 0.00194

Gnomad4 OTH exome AF: 0.00181

GnomAD4 genome AF: 0.00171 AC: 257 AN: 150284 Hom.: 0 Cov.: 26 AF XY: 0.00174 AC XY: 128 AN XY: 73406

Gnomad4 AFR AF: 0.000706

Gnomad4 AMR AF: 0.00370

Gnomad4 ASJ AF: 0.0102

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00108

Gnomad4 NFE AF: 0.00180

Gnomad4 OTH AF: 0.00241

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ABCG1-related disorder Benign:1

Sep 05, 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;