21-42219222-C-CCCGCCG

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_016818.3(ABCG1):​c.-14_-9dupGCCGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 1,468,542 control chromosomes in the GnomAD database, including 856 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.038 (154 hom., cov: 26)
  • Exomes 𝑓: 0.041 (702 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 Benign. Variant got -9 ACMG points.

• BP6: Variant 21-42219222-C-CCCGCCG is Benign according to our data. Variant chr21-42219222-C-CCCGCCG is described in ClinVar as [Benign]. Clinvar id is 3037187.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0376 (5652/150262) while in subpopulation NFE AF= 0.0504 (3396/67326). AF 95% confidence interval is 0.049. There are 154 homozygotes in gnomad4. There are 2622 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 154 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 5649 AN: 150158 Hom.: 153 Cov.: 26

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.0730

Gnomad AMR AF: 0.0356

Gnomad ASJ AF: 0.0365

Gnomad EAS AF: 0.000589

Gnomad SAS AF: 0.0256

Gnomad FIN AF: 0.0241

Gnomad MID AF: 0.0705

Gnomad NFE AF: 0.0504

Gnomad OTH AF: 0.0433

GnomAD3 exomes AF: 0.0209 AC: 1595 AN: 76150 Hom.: 14 AF XY: 0.0224 AC XY: 957 AN XY: 42682

Gnomad AFR exome AF: 0.00886

Gnomad AMR exome AF: 0.00898

Gnomad ASJ exome AF: 0.0236

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0201

Gnomad FIN exome AF: 0.0196

Gnomad NFE exome AF: 0.0301

Gnomad OTH exome AF: 0.0272

GnomAD4 exome AF: 0.0406 AC: 53585 AN: 1318280 Hom.: 702 Cov.: 20 AF XY: 0.0406 AC XY: 26450 AN XY: 651180

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.0143

Gnomad4 ASJ exome AF: 0.0365

Gnomad4 EAS exome AF: 0.000357

Gnomad4 SAS exome AF: 0.0295

Gnomad4 FIN exome AF: 0.0222

Gnomad4 NFE exome AF: 0.0447

Gnomad4 OTH exome AF: 0.0378

GnomAD4 genome AF: 0.0376 AC: 5652 AN: 150262 Hom.: 154 Cov.: 26 AF XY: 0.0357 AC XY: 2622 AN XY: 73394

Gnomad4 AFR AF: 0.0254

Gnomad4 AMR AF: 0.0356

Gnomad4 ASJ AF: 0.0365

Gnomad4 EAS AF: 0.000591

Gnomad4 SAS AF: 0.0258

Gnomad4 FIN AF: 0.0241

Gnomad4 NFE AF: 0.0504

Gnomad4 OTH AF: 0.0433

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ABCG1-related disorder Benign:1

Nov 21, 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;