chr21-42219222-C-CCCGCCGCCGCCGCCG

Position:

• chr21-42219222-C-CCCGCCGCCGCCGCCG

Variant summary

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

The NM_016818.3(ABCG1):​c.-23_-9dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 150,282 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0030 (3 hom., cov: 26)
  • Exomes 𝑓: 0.00012 (0 hom.)
  • Failed GnomAD Quality Control
• 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-CCCGCCGCCGCCGCCG is Benign according to our data. Variant chr21-42219222-C-CCCGCCGCCGCCGCCG is described in ClinVar as [Benign]. Clinvar id is 3053330.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG1	NM_016818.3	c.-23_-9dup		5_prime_UTR_variant	1/15	ENST00000398449.8
LOC105372814	XR_937748.4	n.121+927_121+928insCGGCGGCGGCGGCGG		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG1	ENST00000398449.8	c.-23_-9dup		5_prime_UTR_variant	1/15	1	NM_016818.3	P1

Frequencies

GnomAD3 genomes AF: 0.00298 AC: 447 AN: 150178 Hom.: 3 Cov.: 26

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000530

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.0000445

Gnomad OTH AF: 0.00243

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000125 AC: 165 AN: 1323790 Hom.: 0 Cov.: 20 AF XY: 0.000122 AC XY: 80 AN XY: 653822

Gnomad4 AFR exome AF: 0.00447

Gnomad4 AMR exome AF: 0.0000661

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000267

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000125

Gnomad4 OTH exome AF: 0.000457

GnomAD4 genome AF: 0.00300 AC: 451 AN: 150282 Hom.: 3 Cov.: 26 AF XY: 0.00290 AC XY: 213 AN XY: 73406

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.000529

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000446

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 08, 2020

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;