NM_005502.4:c.3159T>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005502.4(ABCA1):c.3159T>G(p.Val1053Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00999 in 1,614,208 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 3 hom., cov: 32)

Exomes 𝑓: 0.010 ( 98 hom. )

Consequence

ABCA1
NM_005502.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.148

Publications

8 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 9-104819668-A-C is Benign according to our data. Variant chr9-104819668-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 364421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.148 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00735 (1119/152314) while in subpopulation NFE AF = 0.0118 (801/68022). AF 95% confidence interval is 0.0111. There are 3 homozygotes in GnomAd4. There are 505 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005502.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	NM_005502.4	MANE Select	c.3159T>G	p.Val1053Val	synonymous	Exon 22 of 50	NP_005493.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA1	ENST00000374736.8	TSL:1 MANE Select	c.3159T>G	p.Val1053Val	synonymous	Exon 22 of 50	ENSP00000363868.3	O95477
	ABCA1	ENST00000678995.1		c.3159T>G	p.Val1053Val	synonymous	Exon 22 of 50	ENSP00000504612.1	A0A7I2V5U0

Frequencies

GnomAD3 genomes

AF:

0.00735

AC:

1119

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00510

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00750

AC:

1887

AN:

251452

AF XY:

0.00746

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00367

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0115

Gnomad NFE exome

AF:

0.0112

Gnomad OTH exome

AF:

0.00961

GnomAD4 exome

AF:

0.0103

AC:

15012

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

7273

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00143

AC:

AN:

33480

American (AMR)

AF:

0.00434

AC:

194

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00168

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00428

AC:

369

AN:

86258

European-Finnish (FIN)

AF:

0.0116

AC:

619

AN:

53420

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0118

AC:

13172

AN:

1112012

Other (OTH)

AF:

0.00922

AC:

557

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

946

1892

2838

3784

4730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

498

996

1494

1992

2490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00735

AC:

1119

AN:

152314

Hom.:

Cov.:

AF XY:

0.00678

AC XY:

505

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

41558

American (AMR)

AF:

0.00510

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00331

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0105

AC:

112

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0118

AC:

801

AN:

68022

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

124

187

249

311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00872

Hom.:

Bravo

AF:

0.00648

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0101

EpiControl

AF:

0.0108

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Cardiovascular phenotype (1)

Hypoalphalipoproteinemia, primary, 1 (1)

Tangier disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.6

(source)

DANN

Benign

0.74

PhyloP100

0.15

Mutation Taster

=83/17

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over