NM_001288985.2:c.4468A>G

Variant names:

• chr17-68875636-T-C
• rs146578986
• NM_001288985.2:c.4468A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001288985.2(ABCA8):​c.4468A>G​(p.Ile1490Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCA8 NM_001288985.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.96

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]

LOC105371874 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40121293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA8	NM_001288985.2	c.4468A>G	p.Ile1490Val	missense_variant	Exon 36 of 40	ENST00000586539.6	NP_001275914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA8	ENST00000586539.6	c.4468A>G	p.Ile1490Val	missense_variant	Exon 36 of 40	1	NM_001288985.2	ENSP00000467271.1
ABCA8	ENST00000430352.6	c.4453A>G	p.Ile1485Val	missense_variant	Exon 35 of 39	1		ENSP00000402814.3
ABCA8	ENST00000269080.6	c.4348A>G	p.Ile1450Val	missense_variant	Exon 34 of 38	1		ENSP00000269080.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251202 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.095	T;T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Pathogenic	0.92	D
MutationAssessor	Benign	1.3	L;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.77	N;.;.
REVEL	Uncertain	0.49
Sift	Benign	0.086	T;.;.
Sift4G	Uncertain	0.026	D;D;D
Polyphen		0.49	P;.;.
Vest4		0.43
MutPred		0.55		Gain of MoRF binding (P = 0.112);.;.;
MVP		0.60
MPC		0.068
ClinPred		0.76	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.091
gMVP		0.12

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: rs146578986; hg19: chr17-66871777;