4-99574424-A-T

Variant names:

• chr4-99574424-A-T
• rs1800803
• NM_000253.4:c.-101-385A>T

Variant summary

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

The NM_000253.4(MTTP):​c.-101-385A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,048 control chromosomes in the GnomAD database, including 15,298 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 0.42 (15298 hom., cov: 32)
• Consequence: MTTP NM_000253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000253.4. 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_000253.4		c.-101-385A>T		intron	N/A	NP_000244.2
	MTTP	NM_001300785.2		c.-188-7481A>T		intron	N/A	NP_001287714.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTTP	ENST00000457717.6	TSL:5	c.-101-385A>T		intron	N/A	ENSP00000400821.1
	MTTP	ENST00000511045.6	TSL:2	c.-188-7481A>T		intron	N/A	ENSP00000427679.2
	MTTP	ENST00000511610.6	TSL:4	c.-101-385A>T		intron	N/A	ENSP00000422178.2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64472 AN: 151930 Hom.: 15259 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.425 AC: 64557 AN: 152048 Hom.: 15298 Cov.: 32 AF XY: 0.419 AC XY: 31118 AN XY: 74326

African (AFR) AF: 0.648 AC: 26857 AN: 41458

American (AMR) AF: 0.352 AC: 5378 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1728 AN: 3470

East Asian (EAS) AF: 0.334 AC: 1725 AN: 5168

South Asian (SAS) AF: 0.422 AC: 2037 AN: 4822

European-Finnish (FIN) AF: 0.250 AC: 2649 AN: 10576

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22655 AN: 67958

Other (OTH) AF: 0.438 AC: 925 AN: 2110

Alfa AF: 0.376 Hom.: 1486

Bravo AF: 0.437

Asia WGS AF: 0.423 AC: 1465 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.094
DANN	Benign	0.36
PhyloP100		-0.87
PromoterAI		-0.00030	Neutral
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: rs1800803; hg19: chr4-100495581;