rs4147983

Variant names:

• chr17-68922688-G-A
• rs4147983
• NM_001288985.2:c.1443-388C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288985.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA8	NM_001288985.2	MANE Select	c.1443-388C>T		intron	N/A	NP_001275914.1	O94911-3
	ABCA8	NM_001288986.2		c.1443-388C>T		intron	N/A	NP_001275915.1	A0A0A0MSU4
	ABCA8	NM_007168.4		c.1443-388C>T		intron	N/A	NP_009099.1	O94911-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA8	ENST00000586539.6	TSL:1 MANE Select	c.1443-388C>T		intron	N/A	ENSP00000467271.1	O94911-3
	ABCA8	ENST00000430352.6	TSL:1	c.1443-388C>T		intron	N/A	ENSP00000402814.3	A0A0A0MSU4
	ABCA8	ENST00000269080.6	TSL:1	c.1443-388C>T		intron	N/A	ENSP00000269080.1	O94911-1

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

African (AFR) AF: 0.188 AC: 7785 AN: 41448

American (AMR) AF: 0.0397 AC: 607 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 28 AN: 3470

East Asian (EAS) AF: 0.180 AC: 930 AN: 5174

South Asian (SAS) AF: 0.0748 AC: 360 AN: 4810

European-Finnish (FIN) AF: 0.0665 AC: 704 AN: 10584

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0183 AC: 1242 AN: 68000

Other (OTH) AF: 0.0593 AC: 125 AN: 2108

Alfa AF: 0.0372 Hom.: 1330

Bravo AF: 0.0799

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.73
PhyloP100		-0.35
Mutation Taster		=100/0	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: rs4147983; hg19: chr17-66918829;