rs4147983

Positions:

• chr17-68922688-G-A
• chr17-68922688-G-T

Variant summary

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

The NM_001288985.2(ABCA8):​c.1443-388C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 152,096 control chromosomes in the GnomAD database, including 905 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 0.078 (905 hom., cov: 30)
• Consequence: ABCA8 NM_001288985.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA8	NM_001288985.2	c.1443-388C>T		intron_variant		ENST00000586539.6	NP_001275914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA8	ENST00000586539.6	c.1443-388C>T		intron_variant		1	NM_001288985.2	ENSP00000467271.1

Frequencies

GnomAD3 genomes AF: 0.0774 AC: 11757 AN: 151978 Hom.: 899 Cov.: 30

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0397

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.0750

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0585

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

GnomAD4 genome AF: 0.0775 AC: 11795 AN: 152096 Hom.: 905 Cov.: 30 AF XY: 0.0795 AC XY: 5910 AN XY: 74370

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.0397

Gnomad4 ASJ AF: 0.00807

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.0748

Gnomad4 FIN AF: 0.0665

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.0593

Alfa AF: 0.0288 Hom.: 355

Bravo AF: 0.0799

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.73

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: rs4147983; hg19: chr17-66918829;