rs17029173

Variant names:

• chr4-99588164-T-G
• rs17029173
• NM_001386140.1:c.394-1479T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• abetalipoproteinemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, PanelApp Australia, G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MTTP	NM_001386140.1	c.394-1479T>G		intron_variant	Intron 3 of 17	ENST00000265517.10	NP_001373069.1
MTTP	NM_000253.4	c.394-1479T>G		intron_variant	Intron 4 of 18		NP_000244.2
MTTP	NM_001300785.2	c.145-1479T>G		intron_variant	Intron 3 of 17		NP_001287714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTTP	ENST00000265517.10	c.394-1479T>G		intron_variant	Intron 3 of 17	1	NM_001386140.1	ENSP00000265517.5
MTTP	ENST00000457717.6	c.394-1479T>G		intron_variant	Intron 4 of 18	5		ENSP00000400821.1
MTTP	ENST00000511045.6	c.145-1479T>G		intron_variant	Intron 3 of 17	2		ENSP00000427679.2

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

African (AFR) AF: 0.249 AC: 10348 AN: 41490

American (AMR) AF: 0.157 AC: 2398 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1076 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0934 AC: 450 AN: 4818

European-Finnish (FIN) AF: 0.108 AC: 1148 AN: 10610

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10758 AN: 67962

Other (OTH) AF: 0.186 AC: 392 AN: 2112

Alfa AF: 0.172 Hom.: 3491

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
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17029173; hg19: chr4-100509321;