Genetic Variant ABCA7:p.Val915Val (chr19-1051215-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_019112.4(ABCA7):c.2745A>G(p.Val915Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,610,496 control chromosomes in the GnomAD database, including 98,250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9288 hom., cov: 32)

Exomes 𝑓: 0.34 ( 88962 hom. )

Consequence

ABCA7
NM_019112.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -6.55

Variant links:

Genes affected

ABCA7 (HGNC:37): (ATP binding cassette subfamily A member 7) The 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 intra-cellular 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 full transporter has been detected predominantly in myelo-lymphatic tissues with the highest expression in peripheral leukocytes, thymus, spleen, and bone marrow. The function of this protein is not yet known; however, the expression pattern suggests a role in lipid homeostasis in cells of the immune system. [provided by RefSeq, Jul 2008]

ABCA7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 19-1051215-A-G is Benign according to our data. Variant chr19-1051215-A-G is described in ClinVar as [Benign]. Clinvar id is 1241058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA7	NM_019112.4 link	c.2745A>G	p.Val915Val	synonymous_variant	Exon 20 of 47	ENST00000263094.11	NP_061985.2	Q8IZY2-1B3KUJ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCA7	ENST00000263094.11 link	c.2745A>G	p.Val915Val	synonymous_variant	Exon 20 of 47	5	NM_019112.4	ENSP00000263094.6	Q8IZY2-1
ABCA7	ENST00000433129.6 link	n.3425A>G		non_coding_transcript_exon_variant	Exon 19 of 44	1
ABCA7	ENST00000435683.7 link	n.216A>G		non_coding_transcript_exon_variant	Exon 3 of 29	5		ENSP00000465322.2	A0A6E1ZGS3

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52467

AN:

151884

Hom.:

9276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.338

GnomAD3 exomes

AF:

0.337

AC:

83406

AN:

247622

Hom.:

14833

AF XY:

0.332

AC XY:

44712

AN XY:

134514

show subpopulations

Gnomad AFR exome

AF:

0.366

Gnomad AMR exome

AF:

0.399

Gnomad ASJ exome

AF:

0.398

Gnomad EAS exome

AF:

0.125

Gnomad SAS exome

AF:

0.259

Gnomad FIN exome

AF:

0.357

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.347

GnomAD4 exome

AF:

0.344

AC:

502146

AN:

1458494

Hom.:

88962

Cov.:

AF XY:

0.342

AC XY:

248476

AN XY:

725546

show subpopulations

Gnomad4 AFR exome

AF:

0.366

Gnomad4 AMR exome

AF:

0.393

Gnomad4 ASJ exome

AF:

0.401

Gnomad4 EAS exome

AF:

0.106

Gnomad4 SAS exome

AF:

0.262

Gnomad4 FIN exome

AF:

0.357

Gnomad4 NFE exome

AF:

0.355

Gnomad4 OTH exome

AF:

0.332

GnomAD4 genome

AF:

0.345

AC:

52506

AN:

152002

Hom.:

9288

Cov.:

AF XY:

0.341

AC XY:

25322

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.366

Gnomad4 AMR

AF:

0.369

Gnomad4 ASJ

AF:

0.409

Gnomad4 EAS

AF:

0.121

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.338

Gnomad4 NFE

AF:

0.351

Gnomad4 OTH

AF:

0.334

Alfa

AF:

0.351

Hom.:

16889

Bravo

AF:

0.352

Asia WGS

AF:

0.197

AC:

687

AN:

3478

EpiCase

AF:

0.354

EpiControl

AF:

0.364

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 21, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.015

DANN

Benign

0.44

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