chr17-68931279-C-T

Position:

• chr17-68931279-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.797+1009G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,032 control chromosomes in the GnomAD database, including 14,571 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 0.40 (14571 hom., cov: 32)
• Consequence: ABCA8 NM_001288985.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA8	NM_001288985.2	c.797+1009G>A		intron_variant		ENST00000586539.6	NP_001275914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA8	ENST00000586539.6	c.797+1009G>A		intron_variant		1	NM_001288985.2	ENSP00000467271.1
ABCA8	ENST00000430352.6	c.797+1009G>A		intron_variant		1		ENSP00000402814.3
ABCA8	ENST00000269080.6	c.797+1009G>A		intron_variant		1		ENSP00000269080.1
ABCA8	ENST00000541225.5	n.808+1009G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60880 AN: 151914 Hom.: 14574 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.404

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.400 AC: 60869 AN: 152032 Hom.: 14571 Cov.: 32 AF XY: 0.399 AC XY: 29631 AN XY: 74318

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.503

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.400

Alfa AF: 0.508 Hom.: 15490

Bravo AF: 0.374

Asia WGS AF: 0.341 AC: 1187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Benign	0.83

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: rs11656365; hg19: chr17-66927420;