Variant 9-137008345-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001606.5(ABCA2):c.7275+71G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 1,525,942 control chromosomes in the GnomAD database, including 700,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 65974 hom., cov: 33)

Exomes 𝑓: 0.96 ( 634650 hom. )

Consequence

ABCA2
NM_001606.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.49

Variant links:

Genes affected

ABCA2 (HGNC:32): (ATP binding cassette subfamily A member 2) 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. This protein is highly expressed in brain tissue and may play a role in macrophage lipid metabolism and neural development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ABCA2 links:

ABCA2 (HGNC:):

ABCA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 9-137008345-C-G is Benign according to our data. Variant chr9-137008345-C-G is described in ClinVar as [Benign]. Clinvar id is 1185355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ABCA2	NM_001606.5 linkuse as main transcript	c.7275+71G>C	intron_variant	ENST00000341511.11	NP_001597.2	Q9BZC7-3
ABCA2	NM_212533.3 linkuse as main transcript	c.7365+71G>C	intron_variant		NP_997698.1	Q9BZC7-4
ABCA2	NM_001411042.1 linkuse as main transcript	c.7272+71G>C	intron_variant		NP_001397971.1
ABCA2	XM_047422921.1 linkuse as main transcript	c.7362+71G>C	intron_variant		XP_047278877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA2	ENST00000341511.11 linkuse as main transcript	c.7275+71G>C		intron_variant		5	NM_001606.5	ENSP00000344155.6		Q9BZC7-3

Frequencies

GnomAD3 genomes

AF:

0.929

AC:

141339

AN:

152120

Hom.:

65941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.833

Gnomad AMI

AF:

0.986

Gnomad AMR

AF:

0.962

Gnomad ASJ

AF:

0.959

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.978

Gnomad FIN

AF:

0.966

Gnomad MID

AF:

0.978

Gnomad NFE

AF:

0.963

Gnomad OTH

AF:

0.944

GnomAD3 exomes

AF:

0.964

AC:

135526

AN:

140530

Hom.:

65438

AF XY:

0.966

AC XY:

73408

AN XY:

75966

show subpopulations

Gnomad AFR exome

AF:

0.830

Gnomad AMR exome

AF:

0.976

Gnomad ASJ exome

AF:

0.963

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.973

Gnomad FIN exome

AF:

0.973

Gnomad NFE exome

AF:

0.964

Gnomad OTH exome

AF:

0.967

GnomAD4 exome

AF:

0.961

AC:

1320048

AN:

1373704

Hom.:

634650

Cov.:

AF XY:

0.961

AC XY:

652794

AN XY:

678944

show subpopulations

Gnomad4 AFR exome

AF:

0.828

Gnomad4 AMR exome

AF:

0.975

Gnomad4 ASJ exome

AF:

0.962

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.975

Gnomad4 FIN exome

AF:

0.971

Gnomad4 NFE exome

AF:

0.962

Gnomad4 OTH exome

AF:

0.958

GnomAD4 genome

AF:

0.929

AC:

141430

AN:

152238

Hom.:

65974

Cov.:

AF XY:

0.933

AC XY:

69452

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.833

Gnomad4 AMR

AF:

0.962

Gnomad4 ASJ

AF:

0.959

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.978

Gnomad4 FIN

AF:

0.966

Gnomad4 NFE

AF:

0.963

Gnomad4 OTH

AF:

0.945

Alfa

AF:

0.950

Hom.:

12085

Bravo

AF:

0.925

Asia WGS

AF:

0.976

AC:

3394

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Intellectual developmental disorder with poor growth and with or without seizures or ataxia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.43

DANN

Benign

0.39

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

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