17-68886325-T-G

Variant names:

• chr17-68886325-T-G
• rs4148005
• NM_001288985.2:c.3429+692A>C

Variant summary

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

The NM_001288985.2(ABCA8):​c.3429+692A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,954 control chromosomes in the GnomAD database, including 12,441 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 (12441 hom., cov: 32)
• Consequence: ABCA8 NM_001288985.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA8	NM_001288985.2	c.3429+692A>C		intron_variant	Intron 26 of 39	ENST00000586539.6	NP_001275914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA8	ENST00000586539.6	c.3429+692A>C		intron_variant	Intron 26 of 39	1	NM_001288985.2	ENSP00000467271.1
ABCA8	ENST00000430352.6	c.3429+692A>C		intron_variant	Intron 25 of 38	1		ENSP00000402814.3
ABCA8	ENST00000269080.6	c.3309+692A>C		intron_variant	Intron 24 of 37	1		ENSP00000269080.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59192 AN: 151836 Hom.: 12425 Cov.: 32

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.390 AC: 59253 AN: 151954 Hom.: 12441 Cov.: 32 AF XY: 0.389 AC XY: 28874 AN XY: 74284

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.385

Alfa AF: 0.331 Hom.: 4128

Bravo AF: 0.401

Asia WGS AF: 0.363 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.39

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: rs4148005; hg19: chr17-66882466;