Genetic Variant ABCG1:c.42+1933G>A (chr21-42221237-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016818.3(ABCG1):c.42+1933G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,162 control chromosomes in the GnomAD database, including 2,153 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2153 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ABCG1
NM_016818.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.530

Publications

9 publications found

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:

RNA5SP492 (HGNC:43392): (RNA, 5S ribosomal pseudogene 492)

RNA5SP492 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016818.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ABCG1	NM_016818.3	MANE Select	c.42+1933G>A	intron	N/A	NP_058198.2
ABCG1	NM_004915.4		c.42+1933G>A	intron	N/A	NP_004906.3
ABCG1	NM_207174.1		c.75+1191G>A	intron	N/A	NP_997057.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ABCG1	ENST00000398449.8	TSL:1 MANE Select	c.42+1933G>A	intron	N/A	ENSP00000381467.3
ABCG1	ENST00000361802.7	TSL:1	c.42+1933G>A	intron	N/A	ENSP00000354995.2
ABCG1	ENST00000343687.7	TSL:1	c.75+1191G>A	intron	N/A	ENSP00000339744.3

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24846

AN:

152044

Hom.:

2148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.159

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.163

AC:

24860

AN:

152162

Hom.:

2153

Cov.:

AF XY:

0.168

AC XY:

12504

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.153

AC:

6358

AN:

41494

American (AMR)

AF:

0.203

AC:

3100

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

661

AN:

3470

East Asian (EAS)

AF:

0.239

AC:

1238

AN:

5186

South Asian (SAS)

AF:

0.155

AC:

750

AN:

4826

European-Finnish (FIN)

AF:

0.264

AC:

2796

AN:

10574

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9381

AN:

67998

Other (OTH)

AF:

0.157

AC:

331

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1069

2138

3208

4277

5346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.145

Hom.:

2791

Bravo

AF:

0.160

Asia WGS

AF:

0.197

AC:

684

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.6

(source)

DANN

Benign

0.50

PhyloP100

-0.53

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over