rs1057613

Positions:

• chr4-99583828-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000265517.10(MTTP):​c.393+311G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 506,028 control chromosomes in the GnomAD database, including 81,833 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.60 (30340 hom., cov: 32)
  • Exomes 𝑓: 0.52 (51493 hom.)
• Consequence: MTTP ENST00000265517.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 4-99583828-G-A is Benign according to our data. Variant chr4-99583828-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTTP	NM_001386140.1	c.393+311G>A		intron_variant		ENST00000265517.10	NP_001373069.1
MTTP	NM_000253.4	c.393+311G>A		intron_variant			NP_000244.2
MTTP	NM_001300785.2	c.144+311G>A		intron_variant			NP_001287714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTTP	ENST00000422897.6	c.*248G>A		3_prime_UTR_variant	3/3	1		ENSP00000407350
MTTP	ENST00000265517.10	c.393+311G>A		intron_variant		1	NM_001386140.1	ENSP00000265517	P1
MTTP	ENST00000457717.6	c.393+311G>A		intron_variant		5		ENSP00000400821	P1
MTTP	ENST00000511045.6	c.144+311G>A		intron_variant		2		ENSP00000427679

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90416 AN: 151812 Hom.: 30294 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.520 AC: 183982 AN: 354098 Hom.: 51493 Cov.: 2 AF XY: 0.524 AC XY: 97229 AN XY: 185408

Gnomad4 AFR exome AF: 0.904

Gnomad4 AMR exome AF: 0.411

Gnomad4 ASJ exome AF: 0.701

Gnomad4 EAS exome AF: 0.839

Gnomad4 SAS exome AF: 0.617

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.466

Gnomad4 OTH exome AF: 0.530

GnomAD4 genome AF: 0.596 AC: 90503 AN: 151930 Hom.: 30340 Cov.: 32 AF XY: 0.589 AC XY: 43755 AN XY: 74234

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.605

Alfa AF: 0.504 Hom.: 9632

Bravo AF: 0.617

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
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: rs1057613; hg19: chr4-100504985;