17-69105577-C-T

Variant names:

• chr17-69105577-C-T
• rs7212506
• NM_080284.3:c.2625G>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.2625G>A​(p.Met875Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 1,559,994 control chromosomes in the GnomAD database, including 649,929 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.79 (50556 hom., cov: 31)
  • Exomes 𝑓: 0.92 (599373 hom.)
• Consequence: ABCA6 NM_080284.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 36 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=1.184725E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA6	NM_080284.3	c.2625G>A	p.Met875Ile	missense_variant	Exon 20 of 39	ENST00000284425.7	NP_525023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA6	ENST00000284425.7	c.2625G>A	p.Met875Ile	missense_variant	Exon 20 of 39	1	NM_080284.3	ENSP00000284425.1
ABCA6	ENST00000590311.5	n.6521G>A		non_coding_transcript_exon_variant	Exon 5 of 5	1
ABCA6	ENST00000589803.5	n.1620G>A		non_coding_transcript_exon_variant	Exon 9 of 9	5

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119742 AN: 151948 Hom.: 50561 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.830

GnomAD2 exomes AF: 0.878 AC: 217200 AN: 247348 AF XY: 0.892

Gnomad AFR exome AF: 0.445

Gnomad AMR exome AF: 0.804

Gnomad ASJ exome AF: 0.930

Gnomad EAS exome AF: 0.852

Gnomad FIN exome AF: 0.912

Gnomad NFE exome AF: 0.944

Gnomad OTH exome AF: 0.899

GnomAD4 exome AF: 0.919 AC: 1293811 AN: 1407928 Hom.: 599373 Cov.: 31 AF XY: 0.921 AC XY: 647358 AN XY: 702662

African (AFR) AF: 0.435 AC: 14201 AN: 32654

American (AMR) AF: 0.803 AC: 35378 AN: 44056

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 24074 AN: 25800

East Asian (EAS) AF: 0.871 AC: 34261 AN: 39322

South Asian (SAS) AF: 0.915 AC: 76776 AN: 83920

European-Finnish (FIN) AF: 0.914 AC: 48764 AN: 53332

Middle Eastern (MID) AF: 0.889 AC: 3699 AN: 4162

European-Non Finnish (NFE) AF: 0.942 AC: 1004354 AN: 1066172

Other (OTH) AF: 0.894 AC: 52304 AN: 58510

GnomAD4 genome AF: 0.788 AC: 119764 AN: 152066 Hom.: 50556 Cov.: 31 AF XY: 0.788 AC XY: 58575 AN XY: 74342

African (AFR) AF: 0.456 AC: 18874 AN: 41372

American (AMR) AF: 0.793 AC: 12123 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3231 AN: 3472

East Asian (EAS) AF: 0.871 AC: 4520 AN: 5190

South Asian (SAS) AF: 0.915 AC: 4416 AN: 4824

European-Finnish (FIN) AF: 0.921 AC: 9764 AN: 10602

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64003 AN: 68012

Other (OTH) AF: 0.828 AC: 1748 AN: 2110

Alfa AF: 0.891 Hom.: 216056

Bravo AF: 0.761

TwinsUK AF: 0.941 AC: 3489

ALSPAC AF: 0.944 AC: 3638

ESP6500AA AF: 0.464 AC: 2044

ESP6500EA AF: 0.941 AC: 8090

ExAC AF: 0.876 AC: 106322

Asia WGS AF: 0.875 AC: 3036 AN: 3474

EpiCase AF: 0.943

EpiControl AF: 0.940

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.0060
DANN	Benign	0.51
DEOGEN2	Benign	0.088	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-2.3
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.13
Sift	Benign	0.47	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.015
MutPred		0.24		Gain of catalytic residue at M875 (P = 0.001);
MPC		0.037
ClinPred		0.00099	T
GERP RS		-1.7
Varity_R		0.031
gMVP		0.037
Mutation Taster		=99/1	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: rs7212506; hg19: chr17-67101718; COSMIC: COSV107318144;