Variant chr17-69085137-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_080284.3(ABCA6):c.4075T>C(p.Cys1359Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,612,520 control chromosomes in the GnomAD database, including 272 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.010 ( 16 hom., cov: 32)

Exomes 𝑓: 0.017 ( 256 hom. )

Consequence

ABCA6
NM_080284.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.69

Variant links:

Genes affected

ABCA6 (HGNC:36): (ATP binding cassette subfamily A member 6) 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 and may play a role in macrophage lipid homeostasis. [provided by RefSeq, Jul 2008]

ABCA6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02133444).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0101 (1539/152292) while in subpopulation NFE AF= 0.0183 (1245/68020). AF 95% confidence interval is 0.0175. There are 16 homozygotes in gnomad4. There are 650 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA6	NM_080284.3 linkuse as main transcript	c.4075T>C	p.Cys1359Arg	missense_variant	32/39	ENST00000284425.7	NP_525023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA6	ENST00000284425.7 linkuse as main transcript	c.4075T>C	p.Cys1359Arg	missense_variant	32/39	1	NM_080284.3	ENSP00000284425	P1	Q8N139-1
ABCA6	ENST00000446604.6 linkuse as main transcript	n.1341T>C		non_coding_transcript_exon_variant	11/18	2

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1539

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00355

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00609

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0183

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00931

AC:

2282

AN:

245206

Hom.:

AF XY:

0.00951

AC XY:

1261

AN XY:

132612

show subpopulations

Gnomad AFR exome

AF:

0.00329

Gnomad AMR exome

AF:

0.00294

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00139

Gnomad FIN exome

AF:

0.00517

Gnomad NFE exome

AF:

0.0172

Gnomad OTH exome

AF:

0.00949

GnomAD4 exome

AF:

0.0169

AC:

24679

AN:

1460228

Hom.:

256

Cov.:

AF XY:

0.0163

AC XY:

11871

AN XY:

726342

show subpopulations

Gnomad4 AFR exome

AF:

0.00243

Gnomad4 AMR exome

AF:

0.00342

Gnomad4 ASJ exome

AF:

0.000192

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00118

Gnomad4 FIN exome

AF:

0.00644

Gnomad4 NFE exome

AF:

0.0208

Gnomad4 OTH exome

AF:

0.0142

GnomAD4 genome

AF:

0.0101

AC:

1539

AN:

152292

Hom.:

Cov.:

AF XY:

0.00873

AC XY:

650

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00354

Gnomad4 AMR

AF:

0.00608

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.0183

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.0157

Hom.:

Bravo

AF:

0.0109

TwinsUK

AF:

0.0191

AC:

ALSPAC

AF:

0.0187

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0200

AC:

172

ExAC

AF:

0.00977

AC:

1186

EpiCase

AF:

0.0170

EpiControl

AF:

0.0151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.81

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.021

MetaSVM

Uncertain

0.74

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-11

REVEL

Pathogenic

0.78

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.94

MVP

0.99

MPC

0.32

ClinPred

0.073

GERP RS

4.8

Varity_R

0.99

gMVP

0.76

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over