rs2020927

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005502.4(ABCA1):c.5927+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,519,884 control chromosomes in the GnomAD database, including 26,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 6611 hom., cov: 32)

Exomes 𝑓: 0.15 ( 20144 hom. )

Consequence

ABCA1
NM_005502.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.276

Publications

18 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 9-104790904-A-G is Benign according to our data. Variant chr9-104790904-A-G is described in ClinVar as Benign. ClinVar VariationId is 928662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA1	NM_005502.4 link	c.5927+18T>C		intron_variant	Intron 44 of 49	ENST00000374736.8	NP_005493.2	O95477B7XCW9B2RUU2
NIPSNAP3B	XR_007061325.1 link	n.*5A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA1	ENST00000374736.8 link	c.5927+18T>C		intron_variant	Intron 44 of 49	1	NM_005502.4	ENSP00000363868.3		O95477
ABCA1	ENST00000678995.1 link	c.5933+18T>C		intron_variant	Intron 44 of 49			ENSP00000504612.1		A0A7I2V5U0

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36635

AN:

152004

Hom.:

6600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.0620

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.223

GnomAD2 exomes

AF:

0.182

AC:

45660

AN:

250776

AF XY:

0.177

show subpopulations

Gnomad AFR exome

AF:

0.513

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.428

Gnomad FIN exome

AF:

0.0652

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.149

AC:

203445

AN:

1367762

Hom.:

20144

Cov.:

AF XY:

0.149

AC XY:

102375

AN XY:

686210

show subpopulations

African (AFR)

AF:

0.520

AC:

16374

AN:

31464

American (AMR)

AF:

0.149

AC:

6642

AN:

44562

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

2949

AN:

25554

East Asian (EAS)

AF:

0.413

AC:

16138

AN:

39122

South Asian (SAS)

AF:

0.215

AC:

18093

AN:

84156

European-Finnish (FIN)

AF:

0.0677

AC:

3598

AN:

53140

Middle Eastern (MID)

AF:

0.239

AC:

1334

AN:

5574

European-Non Finnish (NFE)

AF:

0.125

AC:

128155

AN:

1026886

Other (OTH)

AF:

0.177

AC:

10162

AN:

57304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

7556

15111

22667

30222

37778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4926

9852

14778

19704

24630

<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:

0.241

AC:

36690

AN:

152122

Hom.:

6611

Cov.:

AF XY:

0.236

AC XY:

17516

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.501

AC:

20770

AN:

41440

American (AMR)

AF:

0.163

AC:

2497

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

417

AN:

3470

East Asian (EAS)

AF:

0.419

AC:

2166

AN:

5172

South Asian (SAS)

AF:

0.226

AC:

1092

AN:

4826

European-Finnish (FIN)

AF:

0.0620

AC:

657

AN:

10600

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8337

AN:

68006

Other (OTH)

AF:

0.223

AC:

472

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1242

2483

3725

4966

6208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.149

Hom.:

3286

Bravo

AF:

0.260

Asia WGS

AF:

0.366

AC:

1265

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 01, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Aug 12, 2019

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Tangier disease

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.4

(source)

DANN

Benign

0.61

PhyloP100

0.28

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over