Variant chr21-42219222-C-CCCGCCG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_016818.3(ABCG1):c.-14_-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 0.0403 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

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0270

Variant links:

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]

ABCG1 links:

LOC105372814 (HGNC:):

LOC105372814 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	UniProt
ABCG1	NM_016818.3 linkuse as main transcript	c.-14_-9dup		5_prime_UTR_variant	1/15	ENST00000398449.8
LOC105372814	XR_937748.4 linkuse as main transcript	n.121+927_121+928insCGGCGG		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG1	ENST00000398449.8 linkuse as main transcript	c.-14_-9dup		5_prime_UTR_variant	1/15	1	NM_016818.3	P1	P45844-4

Frequencies

GnomAD3 genomes

AF:

0.0376

AC:

5649

AN:

150158

Hom.:

153

Cov.:

show subpopulations

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.:

AF XY:

0.0224

AC XY:

957

AN XY:

42682

show subpopulations

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.:

AF XY:

0.0406

AC XY:

26450

AN XY:

651180

show subpopulations

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.:

AF XY:

0.0357

AC XY:

2622

AN XY:

73394

show subpopulations

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

LINK: link

Submissions by phenotype

ABCG1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 21, 2019

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

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over