rs17029173

chr4-99588164-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386140.1(MTTP):c.394-1479T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,116 control chromosomes in the GnomAD database, including 2,737 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2737 hom., cov: 32)
• Consequence: MTTP NM_001386140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTTP	NM_001386140.1	c.394-1479T>G		intron_variant		ENST00000265517.10
MTTP	NM_000253.4	c.394-1479T>G		intron_variant
MTTP	NM_001300785.2	c.145-1479T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTTP	ENST00000265517.10	c.394-1479T>G		intron_variant		1	NM_001386140.1	P1
MTTP	ENST00000457717.6	c.394-1479T>G		intron_variant		5		P1
MTTP	ENST00000511045.6	c.145-1479T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26923 AN: 151998 Hom.: 2732 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0933

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.188

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.177 AC: 26955 AN: 152116 Hom.: 2737 Cov.: 32 AF XY: 0.173 AC XY: 12875 AN XY: 74386

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0934

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.186

Alfa AF: 0.169 Hom.: 2360

Bravo AF: 0.186

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.2
Dann	Benign	0.32

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

Other links and lift over

dbSNP: rs17029173; hg19: chr4-100509321;