rs4880187

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001606.5(ABCA2):c.7275+71G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 1,525,942 control chromosomes in the GnomAD database, including 700,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 65974 hom., cov: 33)

Exomes 𝑓: 0.96 ( 634650 hom. )

Consequence

ABCA2
NM_001606.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.49

Publications

6 publications found

Variant links:

Genes affected

ABCA2 (HGNC:32): (ATP binding cassette subfamily A member 2) 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. This protein is highly expressed in brain tissue and may play a role in macrophage lipid metabolism and neural development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ABCA2 Gene-Disease associations (from GenCC):

intellectual developmental disorder with poor growth and with or without seizures or ataxia
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
schizophrenia
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ABCA2 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=-0.88).

BP6

Variant 9-137008345-C-G is Benign according to our data. Variant chr9-137008345-C-G is described in ClinVar as Benign. ClinVar VariationId is 1185355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001606.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCA2	NM_001606.5	MANE Select	c.7275+71G>C	intron	N/A	NP_001597.2
ABCA2	NM_212533.3		c.7365+71G>C	intron	N/A	NP_997698.1	Q9BZC7-4
ABCA2	NM_001411042.1		c.7272+71G>C	intron	N/A	NP_001397971.1	Q9BZC7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCA2	ENST00000341511.11	TSL:5 MANE Select	c.7275+71G>C	intron	N/A	ENSP00000344155.6	Q9BZC7-3
ABCA2	ENST00000464157.1	TSL:1	n.336G>C	non_coding_transcript_exon	Exon 2 of 2
ABCA2	ENST00000459850.5	TSL:1	n.7485+71G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.929

AC:

141339

AN:

152120

Hom.:

65941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.833

Gnomad AMI

AF:

0.986

Gnomad AMR

AF:

0.962

Gnomad ASJ

AF:

0.959

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.978

Gnomad FIN

AF:

0.966

Gnomad MID

AF:

0.978

Gnomad NFE

AF:

0.963

Gnomad OTH

AF:

0.944

GnomAD2 exomes

AF:

0.964

AC:

135526

AN:

140530

AF XY:

0.966

show subpopulations

Gnomad AFR exome

AF:

0.830

Gnomad AMR exome

AF:

0.976

Gnomad ASJ exome

AF:

0.963

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.973

Gnomad NFE exome

AF:

0.964

Gnomad OTH exome

AF:

0.967

GnomAD4 exome

AF:

0.961

AC:

1320048

AN:

1373704

Hom.:

634650

Cov.:

AF XY:

0.961

AC XY:

652794

AN XY:

678944

show subpopulations

African (AFR)

AF:

0.828

AC:

25777

AN:

31148

American (AMR)

AF:

0.975

AC:

34778

AN:

35676

Ashkenazi Jewish (ASJ)

AF:

0.962

AC:

24099

AN:

25054

East Asian (EAS)

AF:

1.00

AC:

35640

AN:

35642

South Asian (SAS)

AF:

0.975

AC:

76773

AN:

78708

European-Finnish (FIN)

AF:

0.971

AC:

40731

AN:

41928

Middle Eastern (MID)

AF:

0.971

AC:

5495

AN:

5658

European-Non Finnish (NFE)

AF:

0.962

AC:

1021819

AN:

1062548

Other (OTH)

AF:

0.958

AC:

54936

AN:

57342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

2389

4778

7167

9556

11945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20804

41608

62412

83216

104020

<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:

0.929

AC:

141430

AN:

152238

Hom.:

65974

Cov.:

AF XY:

0.933

AC XY:

69452

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.833

AC:

34563

AN:

41510

American (AMR)

AF:

0.962

AC:

14716

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.959

AC:

3328

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5173

AN:

5176

South Asian (SAS)

AF:

0.978

AC:

4718

AN:

4824

European-Finnish (FIN)

AF:

0.966

AC:

10251

AN:

10612

Middle Eastern (MID)

AF:

0.980

AC:

288

AN:

294

European-Non Finnish (NFE)

AF:

0.963

AC:

65499

AN:

68022

Other (OTH)

AF:

0.945

AC:

1995

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

515

1029

1544

2058

2573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.950

Hom.:

12085

Bravo

AF:

0.925

Asia WGS

AF:

0.976

AC:

3394

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Intellectual developmental disorder with poor growth and with or without seizures or ataxia (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.43

(source)

DANN

Benign

0.39

PhyloP100

-1.5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over