rs11937107

Variant names:

• chr4-99582604-C-T
• rs11937107
• NM_001386140.1:c.249+512C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386140.1(MTTP):​c.249+512C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,988 control chromosomes in the GnomAD database, including 5,372 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 0.26 (5372 hom., cov: 32)
• Consequence: MTTP NM_001386140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386140.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTTP	NM_001386140.1	MANE Select	c.249+512C>T		intron	N/A	NP_001373069.1
	MTTP	NM_000253.4		c.249+512C>T		intron	N/A	NP_000244.2
	MTTP	NM_001300785.2		c.-1+512C>T		intron	N/A	NP_001287714.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTTP	ENST00000265517.10	TSL:1 MANE Select	c.249+512C>T		intron	N/A	ENSP00000265517.5
	MTTP	ENST00000422897.6	TSL:1	c.249+512C>T		intron	N/A	ENSP00000407350.2
	MTTP	ENST00000457717.6	TSL:5	c.249+512C>T		intron	N/A	ENSP00000400821.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39776 AN: 151870 Hom.: 5364 Cov.: 32

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: 0.297

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

GnomAD4 genome AF: 0.262 AC: 39807 AN: 151988 Hom.: 5372 Cov.: 32 AF XY: 0.261 AC XY: 19368 AN XY: 74314

African (AFR) AF: 0.278 AC: 11509 AN: 41460

American (AMR) AF: 0.237 AC: 3622 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1381 AN: 3466

East Asian (EAS) AF: 0.146 AC: 758 AN: 5178

South Asian (SAS) AF: 0.346 AC: 1668 AN: 4814

European-Finnish (FIN) AF: 0.191 AC: 2013 AN: 10562

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17683 AN: 67928

Other (OTH) AF: 0.298 AC: 629 AN: 2112

Alfa AF: 0.256 Hom.: 685

Bravo AF: 0.261

Asia WGS AF: 0.290 AC: 1007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.40
PhyloP100		0.015
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: rs11937107; hg19: chr4-100503761; COSMIC: COSV55504352; COSMIC: COSV55504352;