Genetic Variant ABCA1:c.5122-354C>T (chr9-104796778-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_005502.4(ABCA1):c.5122-354C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,130 control chromosomes in the GnomAD database, including 57,143 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 0.87 ( 57143 hom., cov: 32)

Consequence

ABCA1
NM_005502.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.695

Publications

9 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4 link	c.5122-354C>T		intron_variant	Intron 37 of 49	ENST00000374736.8	NP_005493.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8 link	c.5122-354C>T		intron_variant	Intron 37 of 49	1	NM_005502.4	ENSP00000363868.3
ABCA1	ENST00000678995.1 link	c.5128-354C>T		intron_variant	Intron 37 of 49			ENSP00000504612.1

Frequencies

GnomAD3 genomes

AF:

0.865

AC:

131506

AN:

152012

Hom.:

57092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.785

Gnomad AMI

AF:

0.977

Gnomad AMR

AF:

0.905

Gnomad ASJ

AF:

0.850

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.867

Gnomad FIN

AF:

0.910

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.887

Gnomad OTH

AF:

0.861

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

GnomAD4 genome

AF:

0.865

AC:

131612

AN:

152130

Hom.:

57143

Cov.:

AF XY:

0.867

AC XY:

64508

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.785

AC:

32560

AN:

41474

American (AMR)

AF:

0.905

AC:

13835

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.850

AC:

2947

AN:

3468

East Asian (EAS)

AF:

0.999

AC:

5178

AN:

5182

South Asian (SAS)

AF:

0.867

AC:

4178

AN:

4820

European-Finnish (FIN)

AF:

0.910

AC:

9625

AN:

10580

Middle Eastern (MID)

AF:

0.830

AC:

244

AN:

294

European-Non Finnish (NFE)

AF:

0.887

AC:

60336

AN:

68002

Other (OTH)

AF:

0.862

AC:

1818

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

888

1776

2665

3553

4441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.877

Hom.:

74650

Bravo

AF:

0.861

Asia WGS

AF:

0.943

AC:

3278

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.69

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over