chr4-99582604-C-T

Position:

• chr4-99582604-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTTP	NM_001386140.1	c.249+512C>T		intron_variant		ENST00000265517.10	NP_001373069.1
MTTP	NM_000253.4	c.249+512C>T		intron_variant			NP_000244.2
MTTP	NM_001300785.2	c.-1+512C>T		intron_variant			NP_001287714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTTP	ENST00000265517.10	c.249+512C>T		intron_variant		1	NM_001386140.1	ENSP00000265517	P1

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

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.298

Alfa AF: 0.256 Hom.: 663

Bravo AF: 0.261

Asia WGS AF: 0.290 AC: 1007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.40

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: rs11937107; hg19: chr4-100503761; COSMIC: COSV55504352; COSMIC: COSV55504352;