dbSNP rs2297406: ABCA1:c.5928-690G>A (chr9-104789257-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.5928-690G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,154 control chromosomes in the GnomAD database, including 5,255 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 0.23 ( 5255 hom., cov: 32)

Consequence

ABCA1
NM_005502.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.467

Publications

12 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 links:

NIPSNAP3B (HGNC:23641): (nipsnap homolog 3B) NIPSNAP3B belongs to a family of proteins with putative roles in vesicular trafficking (Buechler et al., 2004 [PubMed 15177564]).[supplied by OMIM, Mar 2008]

NIPSNAP3B 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=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4 link	c.5928-690G>A		intron_variant	Intron 44 of 49	ENST00000374736.8	NP_005493.2	O95477B7XCW9B2RUU2
NIPSNAP3B	XR_007061325.1 link	n.2600C>T		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8 link	c.5928-690G>A		intron_variant	Intron 44 of 49	1	NM_005502.4	ENSP00000363868.3		O95477
ABCA1	ENST00000678995.1 link	c.5934-690G>A		intron_variant	Intron 44 of 49			ENSP00000504612.1		A0A7I2V5U0

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35668

AN:

152036

Hom.:

5253

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0558

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.414

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.220

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

GnomAD4 genome

AF:

0.234

AC:

35672

AN:

152154

Hom.:

5255

Cov.:

AF XY:

0.241

AC XY:

17910

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0556

AC:

2311

AN:

41542

American (AMR)

AF:

0.206

AC:

3145

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

1000

AN:

3472

East Asian (EAS)

AF:

0.253

AC:

1306

AN:

5172

South Asian (SAS)

AF:

0.413

AC:

1990

AN:

4818

European-Finnish (FIN)

AF:

0.364

AC:

3847

AN:

10574

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.311

AC:

21175

AN:

67980

Other (OTH)

AF:

0.223

AC:

471

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1318

2636

3955

5273

6591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.276

Hom.:

11874

Bravo

AF:

0.209

Asia WGS

AF:

0.307

AC:

1065

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.9

(source)

DANN

Benign

0.69

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

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