chr17-69129699-C-T

Variant names:

• chr17-69129699-C-T
• rs4968839
• NM_080284.3:c.844G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080284.3(ABCA6):​c.844G>A​(p.Val282Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,600,192 control chromosomes in the GnomAD database, including 371,833 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (29670 hom., cov: 31)
  • Exomes 𝑓: 0.68 (342163 hom.)
• Consequence: ABCA6 NM_080284.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 39 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.30586E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080284.3. 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
	ABCA6	NM_080284.3	MANE Select	c.844G>A	p.Val282Ile	missense	Exon 7 of 39	NP_525023.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA6	ENST00000284425.7	TSL:1 MANE Select	c.844G>A	p.Val282Ile	missense	Exon 7 of 39	ENSP00000284425.1	Q8N139-1
	ABCA6	ENST00000886836.1		c.844G>A	p.Val282Ile	missense	Exon 7 of 40	ENSP00000556895.1
	ABCA6	ENST00000886838.1		c.844G>A	p.Val282Ile	missense	Exon 7 of 40	ENSP00000556897.1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92419 AN: 151704 Hom.: 29668 Cov.: 31

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.634

GnomAD2 exomes AF: 0.660 AC: 164549 AN: 249280 AF XY: 0.665

Gnomad AFR exome AF: 0.398

Gnomad AMR exome AF: 0.734

Gnomad ASJ exome AF: 0.608

Gnomad EAS exome AF: 0.459

Gnomad FIN exome AF: 0.668

Gnomad NFE exome AF: 0.707

Gnomad OTH exome AF: 0.687

GnomAD4 exome AF: 0.684 AC: 990035 AN: 1448370 Hom.: 342163 Cov.: 31 AF XY: 0.684 AC XY: 493508 AN XY: 721052

African (AFR) AF: 0.390 AC: 12927 AN: 33182

American (AMR) AF: 0.732 AC: 32379 AN: 44230

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 15730 AN: 26000

East Asian (EAS) AF: 0.444 AC: 17511 AN: 39462

South Asian (SAS) AF: 0.673 AC: 57507 AN: 85434

European-Finnish (FIN) AF: 0.670 AC: 35666 AN: 53206

Middle Eastern (MID) AF: 0.701 AC: 4025 AN: 5738

European-Non Finnish (NFE) AF: 0.703 AC: 774243 AN: 1101196

Other (OTH) AF: 0.668 AC: 40047 AN: 59922

GnomAD4 genome AF: 0.609 AC: 92471 AN: 151822 Hom.: 29670 Cov.: 31 AF XY: 0.609 AC XY: 45183 AN XY: 74176

African (AFR) AF: 0.401 AC: 16585 AN: 41320

American (AMR) AF: 0.711 AC: 10838 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2103 AN: 3468

East Asian (EAS) AF: 0.452 AC: 2330 AN: 5152

South Asian (SAS) AF: 0.665 AC: 3199 AN: 4814

European-Finnish (FIN) AF: 0.667 AC: 7039 AN: 10552

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48101 AN: 67956

Other (OTH) AF: 0.635 AC: 1336 AN: 2104

Alfa AF: 0.671 Hom.: 154360

Bravo AF: 0.598

TwinsUK AF: 0.709 AC: 2630

ALSPAC AF: 0.697 AC: 2688

ESP6500AA AF: 0.407 AC: 1793

ESP6500EA AF: 0.698 AC: 5993

ExAC AF: 0.655 AC: 79544

Asia WGS AF: 0.565 AC: 1961 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.3
DANN	Benign	0.75
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0000033	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-2.1	N
PhyloP100		1.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.53	N
REVEL	Benign	0.17
Sift	Benign	0.31	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.036
MPC		0.031
ClinPred		0.0069	T
GERP RS		2.1
Varity_R		0.021
gMVP		0.045
Mutation Taster		=98/2	polymorphism (auto)

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: rs4968839; hg19: chr17-67125840; COSMIC: COSV52636800;