19-1051215-A-G

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

2

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]

Genome browser will be placed here

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
ABCA7NM_019112.4 linkc.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 Appris UniProt
ABCA7ENST00000263094.11 linkc.2745A>G p.Val915Val synonymous_variant Exon 20 of 47 5 NM_019112.4 ENSP00000263094.6 Q8IZY2-1
ABCA7ENST00000433129.6 linkn.3425A>G non_coding_transcript_exon_variant Exon 19 of 44 1
ABCA7ENST00000435683.7 linkn.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.:
32
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.:
62
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.:
32
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.

Other links and lift over

dbSNP: rs3752240; hg19: chr19-1051214; COSMIC: COSV54028986; COSMIC: COSV54028986; API