Variant 4-99564098-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000511045.6(MTTP):c.-328G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,534,238 control chromosomes in the GnomAD database, including 52,761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5374 hom., cov: 32)

Exomes 𝑓: 0.26 ( 47387 hom. )

Consequence

MTTP
ENST00000511045.6 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.05

Variant links:

Genes affected

MTTP (HGNC:7467): (microsomal triglyceride transfer protein) MTP encodes the large subunit of the heterodimeric microsomal triglyceride transfer protein. Protein disulfide isomerase (PDI) completes the heterodimeric microsomal triglyceride transfer protein, which has been shown to play a central role in lipoprotein assembly. Mutations in MTP can cause abetalipoproteinemia. [provided by RefSeq, Jul 2008]

MTTP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.7703257E-4).

BP6

Variant 4-99564098-G-A is Benign according to our data. Variant chr4-99564098-G-A is described in ClinVar as [Benign]. Clinvar id is 347009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-99564098-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTTP	NM_000253.4 linkuse as main transcript	c.-241G>A		upstream_gene_variant			NP_000244.2	P55157-1
MTTP	NM_001300785.2 linkuse as main transcript	c.-328G>A		upstream_gene_variant			NP_001287714.2	P55157B7Z7X3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
MTTP	ENST00000457717.6 linkuse as main transcript	c.-241G>A	5_prime_UTR_variant	1/19	5	ENSP00000400821.1	P55157-1
MTTP	ENST00000511045.6 linkuse as main transcript	c.-328G>A	5_prime_UTR_variant	1/18	2	ENSP00000427679.2	E9PBP6
MTTP	ENST00000511610.6 linkuse as main transcript	c.-407G>A	5_prime_UTR_variant	1/4	4	ENSP00000422178.2	D6R915

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39738

AN:

151884

Hom.:

5366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.295

GnomAD3 exomes

AF:

0.258

AC:

33690

AN:

130628

Hom.:

4731

AF XY:

0.268

AC XY:

19094

AN XY:

71308

show subpopulations

Gnomad AFR exome

AF:

0.280

Gnomad AMR exome

AF:

0.170

Gnomad ASJ exome

AF:

0.407

Gnomad EAS exome

AF:

0.136

Gnomad SAS exome

AF:

0.343

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.281

GnomAD4 exome

AF:

0.258

AC:

356490

AN:

1382236

Hom.:

47387

Cov.:

AF XY:

0.261

AC XY:

178249

AN XY:

682054

show subpopulations

Gnomad4 AFR exome

AF:

0.281

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.398

Gnomad4 EAS exome

AF:

0.153

Gnomad4 SAS exome

AF:

0.341

Gnomad4 FIN exome

AF:

0.191

Gnomad4 NFE exome

AF:

0.255

Gnomad4 OTH exome

AF:

0.269

GnomAD4 genome

AF:

0.262

AC:

39769

AN:

152002

Hom.:

5374

Cov.:

AF XY:

0.260

AC XY:

19336

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.277

Gnomad4 AMR

AF:

0.237

Gnomad4 ASJ

AF:

0.398

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.346

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.297

Alfa

AF:

0.273

Hom.:

1126

Bravo

AF:

0.261

TwinsUK

AF:

0.254

AC:

942

ALSPAC

AF:

0.271

AC:

1045

ExAC

AF:

0.280

AC:

3824

Asia WGS

AF:

0.290

AC:

1006

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Abetalipoproteinaemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.7

DANN

Benign

0.90

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0014

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.00058

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.020

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.033

MutPred

0.85

Gain of stability (P = 0.0242);

ClinPred

0.015

GERP RS

-3.0

gMVP

0.52

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