rs4148008

Positions:

• chr17-68879153-C-G
• chr17-68879153-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288985.2(ABCA8):​c.4039-1474G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,138 control chromosomes in the GnomAD database, including 12,678 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 0.39 (12678 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ABCA8 NM_001288985.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847

Genes affected

ABCA8 (HGNC:38): (ATP binding cassette subfamily A member 8) 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, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. The encoded protein may regulate lipid metabolism and be involved in the formation and maintenance of myelin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ABCA8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA8	NM_001288985.2	c.4039-1474G>C		intron_variant		ENST00000586539.6	NP_001275914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA8	ENST00000586539.6	c.4039-1474G>C		intron_variant		1	NM_001288985.2	ENSP00000467271.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59804 AN: 152020 Hom.: 12663 Cov.: 33

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.388

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.393 AC: 59864 AN: 152138 Hom.: 12678 Cov.: 33 AF XY: 0.393 AC XY: 29238 AN XY: 74366

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.388

Alfa AF: 0.214 Hom.: 491

Bravo AF: 0.403

Asia WGS AF: 0.374 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.48
DANN	Benign	0.36

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: rs4148008; hg19: chr17-66875294;