dbSNP rs3847303: ABCA1:c.161-1803G>A (chr9-104886371-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005502.4(ABCA1):c.161-1803G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,108 control chromosomes in the GnomAD database, including 1,944 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 0.15 ( 1944 hom., cov: 32)

Consequence

ABCA1
NM_005502.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.471

Publications

11 publications found

Variant links:

Genes affected

ABCA1 (HGNC:29): (ATP binding cassette subfamily A member 1) The membrane-associated 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 intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesteral efflux pump in the cellular lipid removal pathway. Mutations in both alleles of this gene cause Tangier disease and familial high-density lipoprotein (HDL) deficiency. [provided by RefSeq, Sep 2019]

ABCA1 Gene-Disease associations (from GenCC):

hypoalphalipoproteinemia, primary, 1
Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Tangier disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
apolipoprotein A-I deficiency
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ABCA1 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=-0.7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4 link	c.161-1803G>A		intron_variant	Intron 3 of 49	ENST00000374736.8	NP_005493.2	O95477B7XCW9B2RUU2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCA1	ENST00000374736.8 link	c.161-1803G>A	intron_variant	Intron 3 of 49	1	NM_005502.4	ENSP00000363868.3	O95477
ABCA1	ENST00000678995.1 link	c.161-1803G>A	intron_variant	Intron 3 of 49			ENSP00000504612.1	A0A7I2V5U0
ABCA1	ENST00000423487.6 link	c.161-1803G>A	intron_variant	Intron 3 of 7	2		ENSP00000416623.2	B1AMI2
ABCA1	ENST00000374733.1 link	c.-20-1803G>A	intron_variant	Intron 2 of 4	2		ENSP00000363865.1	B1AMI1

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22549

AN:

151990

Hom.:

1945

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.0622

Gnomad SAS

AF:

0.0919

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.160

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.148

AC:

22565

AN:

152108

Hom.:

1944

Cov.:

AF XY:

0.144

AC XY:

10694

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.238

AC:

9888

AN:

41470

American (AMR)

AF:

0.118

AC:

1801

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

365

AN:

3472

East Asian (EAS)

AF:

0.0623

AC:

322

AN:

5166

South Asian (SAS)

AF:

0.0909

AC:

438

AN:

4818

European-Finnish (FIN)

AF:

0.101

AC:

1074

AN:

10588

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.120

AC:

8144

AN:

68008

Other (OTH)

AF:

0.160

AC:

338

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

963

1926

2890

3853

4816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.130

Hom.:

5912

Bravo

AF:

0.154

Asia WGS

AF:

0.120

AC:

415

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.5

(source)

DANN

Benign

0.58

PhyloP100

-0.47

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over