NM_001288985.2:c.3429+692A>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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=-0.87).
• 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

African (AFR) AF: 0.552 AC: 22881 AN: 41438

American (AMR) AF: 0.354 AC: 5413 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1406 AN: 3468

East Asian (EAS) AF: 0.416 AC: 2147 AN: 5162

South Asian (SAS) AF: 0.314 AC: 1514 AN: 4820

European-Finnish (FIN) AF: 0.310 AC: 3266 AN: 10552

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.315 AC: 21426 AN: 67932

Other (OTH) AF: 0.385 AC: 809 AN: 2102

Alfa AF: 0.331 Hom.: 4560

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
PhyloP100		0.052
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: rs4148005; hg19: chr17-66882466;