21-42219222-CCCGCCGCCGCCGCCG-C

Position:

• chr21-42219222-CCCGCCGCCGCCGCCG-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_016818.3(ABCG1):​c.-23_-9del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,474,162 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: ABCG1 NM_016818.3 5_prime_UTR
• Clinical Significance: Likely 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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 21-42219222-CCCGCCGCCGCCGCCG-C is Benign according to our data. Variant chr21-42219222-CCCGCCGCCGCCGCCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 3047646.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG1	NM_016818.3	c.-23_-9del		5_prime_UTR_variant	1/15	ENST00000398449.8
LOC105372814	XR_937748.4	n.121+913_121+927del		intron_variant, non_coding_transcript_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150180 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000242 AC: 32 AN: 1323878 Hom.: 0 AF XY: 0.0000336 AC XY: 22 AN XY: 653864

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000662

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000160

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000163

Gnomad4 OTH exome AF: 0.0000183

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150284 Hom.: 0 Cov.: 26 AF XY: 0.0000136 AC XY: 1 AN XY: 73406

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000149

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ABCG1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 25, 2019

This variant is classified as likely 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;