chr4-99574331-G-T

Position:

• chr4-99574331-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000253.4(MTTP):​c.-101-478G>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 152,084 control chromosomes in the GnomAD database, including 5,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5385 hom., cov: 32)
• Consequence: MTTP NM_000253.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.279

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-99574331-G-T is Benign according to our data. Variant chr4-99574331-G-T is described in ClinVar as [Benign]. Clinvar id is 1168852.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
MTTP	NM_000253.4	c.-101-478G>T		intron_variant
MTTP	NM_001300785.2	c.-188-7574G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTTP	ENST00000457717.6	c.-101-478G>T		intron_variant		5		P1
MTTP	ENST00000505094.6	c.-189+3466G>T		intron_variant		4
MTTP	ENST00000511045.6	c.-188-7574G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39816 AN: 151966 Hom.: 5377 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.348

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: 39847 AN: 152084 Hom.: 5385 Cov.: 32 AF XY: 0.261 AC XY: 19383 AN XY: 74366

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.298

Alfa AF: 0.153 Hom.: 313

Bravo AF: 0.261

Asia WGS AF: 0.290 AC: 1006 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.71
DANN	Benign	0.30

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: rs1800591; hg19: chr4-100495488;