Variant chr19-1041541-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP3BP4BP6_Moderate

The NM_019112.4(ABCA7):c.98T>C(p.Leu33Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,613,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

ABCA7
NM_019112.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.75

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_noAF, Cadd, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.35756385).

BP6

Variant 19-1041541-T-C is Benign according to our data. Variant chr19-1041541-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 715315.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA7	NM_019112.4 linkuse as main transcript	c.98T>C	p.Leu33Pro	missense_variant	3/47	ENST00000263094.11	NP_061985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11 linkuse as main transcript	c.98T>C	p.Leu33Pro	missense_variant	3/47	5	NM_019112.4	ENSP00000263094	P1	Q8IZY2-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000227

AC:

AN:

250746

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000404

AC:

AN:

1461236

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726922

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ExAC

AF:

0.000255

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

.;D;.;D;D

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

T;D;D;D;.

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.36

T;T;T;T;T

MetaSVM

Uncertain

0.75

MutationAssessor

Pathogenic

3.4

.;M;.;.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.1

.;D;D;D;D

REVEL

Pathogenic

0.90

Sift

Uncertain

0.0010

.;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

.;D;.;.;D

Vest4

0.85, 0.85

MutPred

0.62

Loss of stability (P = 0.0135);Loss of stability (P = 0.0135);Loss of stability (P = 0.0135);.;Loss of stability (P = 0.0135);

MVP

0.92

MPC

0.67

ClinPred

0.51

GERP RS

4.8

Varity_R

0.90

gMVP

0.87

Splicing

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