1-94083473-A-G

Variant names:

Variant summary

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

The NM_000350.3(ABCA4):c.769-32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,535,706 control chromosomes in the GnomAD database, including 67,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4975 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62242 hom. )

Consequence

ABCA4
NM_000350.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 0.649

Publications

3 publications found

Variant links:

Genes affected

ABCA4 (HGNC:34): (ATP binding cassette subfamily A member 4) 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 a retina-specific ABC transporter with N-retinylidene-PE as a substrate. It is expressed exclusively in retina photoreceptor cells, and the gene product mediates transport of an essental molecule, all-trans-retinal aldehyde (atRAL), across the photoreceptor cell membrane. Mutations in this gene are found in patients diagnosed with Stargardt disease, a form of juvenile-onset macular degeneration. Mutations in this gene are also associated with retinitis pigmentosa-19, cone-rod dystrophy type 3, early-onset severe retinal dystrophy, fundus flavimaculatus, and macular degeneration age-related 2. [provided by RefSeq, Sep 2019]

ABCA4 Gene-Disease associations (from GenCC):

ABCA4-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cone-rod dystrophy 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
severe early-childhood-onset retinal dystrophy
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics
retinitis pigmentosa 19
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Stargardt disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ABCA4 links:

LOC124904222 (HGNC:):

LOC124904222 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=-0.74).

BP6

Variant 1-94083473-A-G is Benign according to our data. Variant chr1-94083473-A-G is described in ClinVar as Benign. ClinVar VariationId is 99507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000350.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA4	NM_000350.3	MANE Select	c.769-32T>C		intron	N/A	NP_000341.2
	ABCA4	NM_001425324.1		c.769-32T>C		intron	N/A	NP_001412253.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA4	ENST00000370225.4	TSL:1 MANE Select	c.769-32T>C		intron	N/A	ENSP00000359245.3
	ABCA4	ENST00000649773.1		c.769-32T>C		intron	N/A	ENSP00000496882.1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36500

AN:

151826

Hom.:

4969

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.256

GnomAD2 exomes

AF:

0.245

AC:

60567

AN:

247468

AF XY:

0.244

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.195

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.293

AC:

405486

AN:

1383762

Hom.:

62242

Cov.:

AF XY:

0.289

AC XY:

199975

AN XY:

693042

show subpopulations

African (AFR)

AF:

0.114

AC:

3607

AN:

31732

American (AMR)

AF:

0.210

AC:

9356

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

6023

AN:

25666

East Asian (EAS)

AF:

0.223

AC:

8746

AN:

39296

South Asian (SAS)

AF:

0.158

AC:

13391

AN:

84638

European-Finnish (FIN)

AF:

0.252

AC:

13014

AN:

51740

Middle Eastern (MID)

AF:

0.168

AC:

940

AN:

5604

European-Non Finnish (NFE)

AF:

0.321

AC:

335038

AN:

1042634

Other (OTH)

AF:

0.266

AC:

15371

AN:

57826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

14576

29152

43728

58304

72880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10524

21048

31572

42096

52620

<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:

0.240

AC:

36524

AN:

151944

Hom.:

4975

Cov.:

AF XY:

0.237

AC XY:

17581

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.120

AC:

4958

AN:

41408

American (AMR)

AF:

0.257

AC:

3922

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

861

AN:

3466

East Asian (EAS)

AF:

0.214

AC:

1106

AN:

5178

South Asian (SAS)

AF:

0.162

AC:

781

AN:

4810

European-Finnish (FIN)

AF:

0.254

AC:

2672

AN:

10540

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.316

AC:

21442

AN:

67962

Other (OTH)

AF:

0.254

AC:

535

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1391

2783

4174

5566

6957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.181

Hom.:

588

Bravo

AF:

0.235

Asia WGS

AF:

0.188

AC:

654

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.6

(source)

DANN

Benign

0.88

PhyloP100

0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over