4-99574424-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTTP	NM_000253.4	c.-101-385A>T		intron_variant
MTTP	NM_001300785.2	c.-188-7481A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTTP	ENST00000457717.6	c.-101-385A>T		intron_variant		5		P1
MTTP	ENST00000505094.6	c.-189+3559A>T		intron_variant		4
MTTP	ENST00000511045.6	c.-188-7481A>T		intron_variant		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

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.438

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.094
Dann	Benign	0.36

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: rs1800803; hg19: chr4-100495581;