rs745075

chr4-99611480-T-C

Variant summary

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

The NM_001386140.1(MTTP):c.1989+27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,612,368 control chromosomes in the GnomAD database, including 11,274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (995 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10279 hom.)
• Consequence: MTTP NM_001386140.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-99611480-T-C is Benign according to our data. Variant chr4-99611480-T-C is described in ClinVar as [Benign]. Clinvar id is 1260037.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-99611480-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTTP	NM_001386140.1	c.1989+27T>C		intron_variant		ENST00000265517.10
MTTP	NM_000253.4	c.1989+27T>C		intron_variant
MTTP	NM_001300785.2	c.1740+27T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTTP	ENST00000265517.10	c.1989+27T>C		intron_variant		1	NM_001386140.1	P1
	ENST00000508578.1	n.128+9407A>G		intron_variant, non_coding_transcript_variant		5
MTTP	ENST00000457717.6	c.1989+27T>C		intron_variant		5		P1
MTTP	ENST00000511045.6	c.1740+27T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15852 AN: 152072 Hom.: 994 Cov.: 32

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0668

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.121

GnomAD3 exomes AF: 0.0971 AC: 24327 AN: 250594 Hom.: 1574 AF XY: 0.0982 AC XY: 13297 AN XY: 135394

Gnomad AFR exome AF: 0.0845

Gnomad AMR exome AF: 0.0705

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0764

Gnomad FIN exome AF: 0.0531

Gnomad NFE exome AF: 0.119

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.112 AC: 164030 AN: 1460178 Hom.: 10279 Cov.: 33 AF XY: 0.112 AC XY: 81298 AN XY: 726504

Gnomad4 AFR exome AF: 0.0864

Gnomad4 AMR exome AF: 0.0744

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.000328

Gnomad4 SAS exome AF: 0.0772

Gnomad4 FIN exome AF: 0.0555

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.104 AC: 15872 AN: 152190 Hom.: 995 Cov.: 32 AF XY: 0.103 AC XY: 7631 AN XY: 74410

Gnomad4 AFR AF: 0.0863

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0669

Gnomad4 FIN AF: 0.0547

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.120

Alfa AF: 0.126 Hom.: 1992

Bravo AF: 0.108

Asia WGS AF: 0.0340 AC: 118 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

GeneDx

Sep 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.0
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs745075; hg19: chr4-100532637;