Variant 17-68876704-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP6_ModerateBS1BS2

The NM_001288985.2(ABCA8):c.4200-1G>C variant causes a splice acceptor change. The variant allele was found at a frequency of 0.00142 in 1,614,136 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 36 hom. )

Consequence

ABCA8
NM_001288985.2 splice_acceptor

Scores

Splicing: ADA: 0.9999

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.94

Variant links:

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 links:

LOC105371874 (HGNC:):

LOC105371874 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 5: Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, Eigen [when BayesDel_addAF, MutationTaster was below the threshold]

BP6

Variant 17-68876704-C-G is Benign according to our data. Variant chr17-68876704-C-G is described in ClinVar as [Benign]. Clinvar id is 769926.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00269 (410/152270) while in subpopulation AMR AF= 0.0242 (370/15292). AF 95% confidence interval is 0.0222. There are 6 homozygotes in gnomad4. There are 237 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA8	NM_001288985.2 linkuse as main transcript	c.4200-1G>C		splice_acceptor_variant		ENST00000586539.6
LOC105371874	XR_001752986.3 linkuse as main transcript	n.1773C>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA8	ENST00000586539.6 linkuse as main transcript	c.4200-1G>C		splice_acceptor_variant		1	NM_001288985.2	P4	O94911-3

Frequencies

GnomAD3 genomes

AF:

0.00267

AC:

406

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00559

AC:

1404

AN:

251316

Hom.:

AF XY:

0.00447

AC XY:

607

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0394

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:

0.00

Gnomad OTH exome

AF:

0.00538

GnomAD4 exome

AF:

0.00129

AC:

1881

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

812

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0401

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.00269

AC:

410

AN:

152270

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

237

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.0242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.000563

Hom.:

Bravo

AF:

0.00454

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00400

AC:

486

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Pathogenic

0.89

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

MutationTaster

Benign

1.0

D;D;D

GERP RS

3.9

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.94

SpliceAI score (max)

1.0

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.57

Position offset: 29

DS_AL_spliceai

1.0

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over