Variant 19-1041972-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_019112.4(ABCA7):c.302T>G(p.Leu101Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00186 in 1,583,254 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 4 hom. )

Consequence

ABCA7
NM_019112.4 missense, splice_region

Scores

Splicing: ADA: 0.1781

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11415154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA7	NM_019112.4 linkuse as main transcript	c.302T>G	p.Leu101Arg	missense_variant, splice_region_variant	4/47	ENST00000263094.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA7	ENST00000263094.11 linkuse as main transcript	c.302T>G	p.Leu101Arg	missense_variant, splice_region_variant	4/47	5	NM_019112.4	P1	Q8IZY2-1

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

156

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

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:

0.00156

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000802

AC:

174

AN:

216986

Hom.:

AF XY:

0.000828

AC XY:

100

AN XY:

120840

show subpopulations

Gnomad AFR exome

AF:

0.0000722

Gnomad AMR exome

AF:

0.000729

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000774

Gnomad NFE exome

AF:

0.00142

Gnomad OTH exome

AF:

0.000950

GnomAD4 exome

AF:

0.00195

AC:

2791

AN:

1430922

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1297

AN XY:

711158

show subpopulations

Gnomad4 AFR exome

AF:

0.000463

Gnomad4 AMR exome

AF:

0.000618

Gnomad4 ASJ exome

AF:

0.0000399

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000143

Gnomad4 NFE exome

AF:

0.00239

Gnomad4 OTH exome

AF:

0.00186

GnomAD4 genome

AF:

0.00102

AC:

156

AN:

152332

Hom.:

Cov.:

AF XY:

0.000940

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.000933

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000233

AC:

ESP6500EA

AF:

0.000827

AC:

ExAC

AF:

0.000639

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Amyotrophic lateral sclerosis

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Human Genetics Bochum, Ruhr University Bochum

Nov 10, 2022

ACMG criteria used to clasify this variant: PS4_SUP, PM2_SUP, PP1_SUP, PP3_SUP -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.080

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;.;T;D

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.53

T;T;T;.

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.8

M;.;.;M

MutationTaster

Benign

0.97

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-4.1

D;D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

0.98

D;.;.;D

Vest4

0.77

MVP

0.70

MPC

0.64

ClinPred

0.13

GERP RS

4.1

Varity_R

0.74

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.18

dbscSNV1_RF

Benign

0.48

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