rs77542162

chr17-69085137-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.69

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA6	NM_080284.3	c.4075T>C	p.Cys1359Arg	missense_variant	32/39	ENST00000284425.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1539 AN: 152174 Hom.: 16 Cov.: 32

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.: 25 AF XY: 0.00951 AC XY: 1261 AN XY: 132612

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.: 32 AF XY: 0.0163 AC XY: 11871 AN XY: 726342

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.: 16 Cov.: 32 AF XY: 0.00873 AC XY: 650 AN XY: 74458

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.: 41

Bravo AF: 0.0109

TwinsUK AF: 0.0191 AC: 71

ALSPAC AF: 0.0187 AC: 72

ESP6500AA AF: 0.00295 AC: 13

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	T
BayesDel_noAF	Uncertain	0.040
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Pathogenic	0.81	D
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.021	T
MetaSVM	Uncertain	0.74	D
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-11	D
REVEL	Pathogenic	0.78
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.94
MVP		0.99
MPC		0.32
ClinPred		0.073	T
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

Other links and lift over

dbSNP: rs77542162; hg19: chr17-67081278; COSMIC: COSV105823100; COSMIC: COSV105823100;