Variant 17-69253570-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The ENST00000392676.8(ABCA5):c.4415+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,604,852 control chromosomes in the GnomAD database, including 360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 23 hom., cov: 32)

Exomes 𝑓: 0.019 ( 337 hom. )

Consequence

ABCA5
ENST00000392676.8 splice_donor_region, intron

Scores

Splicing: ADA: 0.00006409

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.291

Variant links:

Genes affected

ABCA5 (HGNC:35): (ATP binding cassette subfamily A member 5) 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, and White). This encoded 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 gene is clustered among 4 other ABC1 family members on 17q24, but neither the substrate nor the function of this gene is known. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

ABCA5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 17-69253570-C-T is Benign according to our data. Variant chr17-69253570-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3037281.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1816/152262) while in subpopulation NFE AF= 0.0212 (1443/67998). AF 95% confidence interval is 0.0203. There are 23 homozygotes in gnomad4. There are 785 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA5	NM_172232.4 linkuse as main transcript	c.4415+3G>A		splice_donor_region_variant, intron_variant		ENST00000392676.8	NP_758424.1
ABCA5	NM_018672.5 linkuse as main transcript	c.4415+3G>A		splice_donor_region_variant, intron_variant			NP_061142.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA5	ENST00000392676.8 linkuse as main transcript	c.4415+3G>A		splice_donor_region_variant, intron_variant		1	NM_172232.4	ENSP00000376443	P1	Q8WWZ7-1

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1816

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00449

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0212

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.0107

AC:

2692

AN:

250930

Hom.:

AF XY:

0.0110

AC XY:

1490

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.00448

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.00527

Gnomad NFE exome

AF:

0.0198

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.0193

AC:

28032

AN:

1452590

Hom.:

337

Cov.:

AF XY:

0.0186

AC XY:

13427

AN XY:

723364

show subpopulations

Gnomad4 AFR exome

AF:

0.00279

Gnomad4 AMR exome

AF:

0.00503

Gnomad4 ASJ exome

AF:

0.000154

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00115

Gnomad4 FIN exome

AF:

0.00659

Gnomad4 NFE exome

AF:

0.0238

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

AF:

0.0119

AC:

1816

AN:

152262

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

785

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00448

Gnomad4 AMR

AF:

0.00830

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.0212

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.0167

Hom.:

Bravo

AF:

0.0126

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0199

EpiControl

AF:

0.0179

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ABCA5-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 06, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000064

dbscSNV1_RF

Benign

0.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over