rs55860151

Variant names:

• chr1-94021729-AAC-A
• rs55860151
• NM_000350.3:c.4774-17_4774-16delGT

Your query was ambiguous. Multiple possible variants found:

• chr1-94021729-AAC-A
• chr1-94021729-AAC-AACAC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000350.3(ABCA4):​c.4774-17_4774-16delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,611,092 control chromosomes in the GnomAD database, including 35,843 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2664 hom., cov: 29)
  • Exomes 𝑓: 0.21 (33179 hom.)
• Consequence: ABCA4 NM_000350.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.145
• Publications: 9 publications found

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
• age related macular degeneration 2

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-94021729-AAC-A is Benign according to our data. Variant chr1-94021729-AAC-A is described in ClinVar as Benign. ClinVar VariationId is 255923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA4	NM_000350.3	MANE Select	c.4774-17_4774-16delGT		intron	N/A	NP_000341.2	P78363
	ABCA4	NM_001425324.1		c.4552-17_4552-16delGT		intron	N/A	NP_001412253.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA4	ENST00000370225.4	TSL:1 MANE Select	c.4774-17_4774-16delGT		intron	N/A	ENSP00000359245.3	P78363
	ABCA4	ENST00000460514.1	TSL:5	n.268-17_268-16delGT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24797 AN: 152058 Hom.: 2664 Cov.: 29

Gnomad AFR AF: 0.0444

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.195

GnomAD2 exomes AF: 0.210 AC: 52124 AN: 248696 AF XY: 0.213

Gnomad AFR exome AF: 0.0365

Gnomad AMR exome AF: 0.186

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.480

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.214

GnomAD4 exome AF: 0.205 AC: 299657 AN: 1458916 Hom.: 33179 AF XY: 0.206 AC XY: 149879 AN XY: 725924

African (AFR) AF: 0.0373 AC: 1246 AN: 33396

American (AMR) AF: 0.188 AC: 8403 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 5137 AN: 26080

East Asian (EAS) AF: 0.444 AC: 17604 AN: 39654

South Asian (SAS) AF: 0.256 AC: 22075 AN: 86102

European-Finnish (FIN) AF: 0.136 AC: 7242 AN: 53398

Middle Eastern (MID) AF: 0.196 AC: 1131 AN: 5764

European-Non Finnish (NFE) AF: 0.202 AC: 224178 AN: 1109598

Other (OTH) AF: 0.210 AC: 12641 AN: 60282

GnomAD4 genome AF: 0.163 AC: 24799 AN: 152176 Hom.: 2664 Cov.: 29 AF XY: 0.163 AC XY: 12111 AN XY: 74402

African (AFR) AF: 0.0444 AC: 1845 AN: 41542

American (AMR) AF: 0.208 AC: 3185 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 737 AN: 3470

East Asian (EAS) AF: 0.474 AC: 2445 AN: 5160

South Asian (SAS) AF: 0.269 AC: 1296 AN: 4818

European-Finnish (FIN) AF: 0.123 AC: 1300 AN: 10608

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13313 AN: 67964

Other (OTH) AF: 0.194 AC: 410 AN: 2112

Alfa AF: 0.168 Hom.: 440

Bravo AF: 0.164

Asia WGS AF: 0.349 AC: 1213 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Age related macular degeneration 2 (1)
-	-	1	Cone-rod dystrophy 3 (1)
-	-	1	Cone-Rod Dystrophy, Recessive (1)
-	-	1	Macular degeneration (1)
-	-	1	not specified (1)
-	-	1	Retinitis pigmentosa 19 (1)
-	-	1	Retinitis Pigmentosa, Recessive (1)
-	-	1	Severe early-childhood-onset retinal dystrophy (1)
-	-	1	Stargardt Disease, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs55860151; hg19: chr1-94487285; COSMIC: COSV104427044; COSMIC: COSV104427044;