rs7693203

Variant names:

• chr4-99578973-C-T
• rs7693203
• NM_001386140.1:c.62-2932C>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.62-2932C>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 152,042 control chromosomes in the GnomAD database, including 5,392 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 (5392 hom., cov: 32)
• Consequence: MTTP NM_001386140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• Publications: 8 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: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTTP	NM_001386140.1	MANE Select	c.62-2932C>T		intron	N/A	NP_001373069.1	P55157-1
	MTTP	NM_000253.4		c.62-2932C>T		intron	N/A	NP_000244.2	P55157-1
	MTTP	NM_001300785.2		c.-188-2932C>T		intron	N/A	NP_001287714.2	E9PBP6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTTP	ENST00000265517.10	TSL:1 MANE Select	c.62-2932C>T		intron	N/A	ENSP00000265517.5	P55157-1
	MTTP	ENST00000422897.6	TSL:1	c.62-2932C>T		intron	N/A	ENSP00000407350.2	P55157-2
	MTTP	ENST00000457717.6	TSL:5	c.62-2932C>T		intron	N/A	ENSP00000400821.1	P55157-1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39829 AN: 151924 Hom.: 5384 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.190

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: 39860 AN: 152042 Hom.: 5392 Cov.: 32 AF XY: 0.261 AC XY: 19396 AN XY: 74340

African (AFR) AF: 0.278 AC: 11526 AN: 41438

American (AMR) AF: 0.238 AC: 3634 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1385 AN: 3466

East Asian (EAS) AF: 0.147 AC: 754 AN: 5146

South Asian (SAS) AF: 0.347 AC: 1676 AN: 4828

European-Finnish (FIN) AF: 0.190 AC: 2013 AN: 10568

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

European-Non Finnish (NFE) AF: 0.260 AC: 17701 AN: 67988

Other (OTH) AF: 0.298 AC: 627 AN: 2106

Alfa AF: 0.266 Hom.: 2950

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	-0.83
CADD	Benign	1.7
DANN	Benign	0.73
PhyloP100		-0.60
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: rs7693203; hg19: chr4-100500130;