4-99600480-C-T

Position:

• chr4-99600480-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001386140.1(MTTP):​c.1068-85C>T 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 1,373,512 control chromosomes in the GnomAD database, including 9,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (990 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8697 hom.)
• Consequence: MTTP NM_001386140.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.409

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]

ENSG00000248676 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-99600480-C-T is Benign according to our data. Variant chr4-99600480-C-T is described in ClinVar as [Benign]. Clinvar id is 1295322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-99600480-C-T 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	Protein	UniProt
MTTP	NM_001386140.1	c.1068-85C>T		intron_variant		ENST00000265517.10	NP_001373069.1
MTTP	NM_000253.4	c.1068-85C>T		intron_variant			NP_000244.2
MTTP	NM_001300785.2	c.819-85C>T		intron_variant			NP_001287714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTTP	ENST00000265517.10	c.1068-85C>T		intron_variant		1	NM_001386140.1	ENSP00000265517.5
MTTP	ENST00000457717.6	c.1068-85C>T		intron_variant		5		ENSP00000400821.1
MTTP	ENST00000511045.6	c.819-85C>T		intron_variant		2		ENSP00000427679.2
ENSG00000248676	ENST00000508578.1	n.129-4839G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15811 AN: 151844 Hom.: 989 Cov.: 32

Gnomad AFR AF: 0.0854

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0664

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.113 AC: 137693 AN: 1221550 Hom.: 8697 AF XY: 0.112 AC XY: 69380 AN XY: 618930

Gnomad4 AFR exome AF: 0.0869

Gnomad4 AMR exome AF: 0.0739

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.000340

Gnomad4 SAS exome AF: 0.0771

Gnomad4 FIN exome AF: 0.0555

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.104 AC: 15828 AN: 151962 Hom.: 990 Cov.: 32 AF XY: 0.102 AC XY: 7608 AN XY: 74276

Gnomad4 AFR AF: 0.0857

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0665

Gnomad4 FIN AF: 0.0547

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.120

Alfa AF: 0.108 Hom.: 125

Bravo AF: 0.107

Asia WGS AF: 0.0340 AC: 117 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.90
CADD	Benign	0.37
DANN	Benign	0.20

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: rs17533517; hg19: chr4-100521637;