dbSNP rs4147914: ABCA7:p.Leu795Leu (chr19-1049270-G-A) – 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.2385G>A(p.Leu795Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,602,504 control chromosomes in the GnomAD database, including 22,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2227 hom., cov: 30)

Exomes 𝑓: 0.16 ( 20265 hom. )

Consequence

ABCA7
NM_019112.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.50

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=-0.55).

BP6

Variant 19-1049270-G-A is Benign according to our data. Variant chr19-1049270-G-A is described in ClinVar as [Benign]. Clinvar id is 1257803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA7	NM_019112.4 link	c.2385G>A	p.Leu795Leu	synonymous_variant	Exon 18 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.2385G>A	p.Leu795Leu	synonymous_variant	Exon 18 of 47	5	NM_019112.4	ENSP00000263094.6	Q8IZY2-1
ABCA7	ENST00000433129.6 link	n.3065G>A		non_coding_transcript_exon_variant	Exon 17 of 44	1
ABCA7	ENST00000435683.7 link	n.-145G>A		upstream_gene_variant		5		ENSP00000465322.2	A0A6E1ZGS3

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24373

AN:

151786

Hom.:

2217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.380

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.181

GnomAD3 exomes

AF:

0.174

AC:

42184

AN:

242114

Hom.:

4527

AF XY:

0.178

AC XY:

23455

AN XY:

131480

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.222

Gnomad EAS exome

AF:

0.397

Gnomad SAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.158

GnomAD4 exome

AF:

0.156

AC:

226540

AN:

1450600

Hom.:

20265

Cov.:

AF XY:

0.159

AC XY:

114545

AN XY:

720502

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.220

Gnomad4 EAS exome

AF:

0.422

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.175

GnomAD4 genome

AF:

0.161

AC:

24404

AN:

151904

Hom.:

2227

Cov.:

AF XY:

0.162

AC XY:

12008

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.213

Gnomad4 EAS

AF:

0.380

Gnomad4 SAS

AF:

0.290

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.189

Alfa

AF:

0.148

Hom.:

1082

Bravo

AF:

0.157

Asia WGS

AF:

0.343

AC:

1192

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 23, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28171541) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.6

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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