NM_001386140.1:c.1068-85C>T

Variant names:

• chr4-99600480-C-T
• rs17533517
• NM_001386140.1:c.1068-85C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

MTTP Gene-Disease associations (from GenCC):

• abetalipoproteinemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000248676 (HGNC:54189):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1295322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386140.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTTP	NM_001386140.1	MANE Select	c.1068-85C>T		intron	N/A	NP_001373069.1	P55157-1
	MTTP	NM_000253.4		c.1068-85C>T		intron	N/A	NP_000244.2	P55157-1
	MTTP	NM_001300785.2		c.819-85C>T		intron	N/A	NP_001287714.2	E9PBP6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTTP	ENST00000265517.10	TSL:1 MANE Select	c.1068-85C>T		intron	N/A	ENSP00000265517.5	P55157-1
	MTTP	ENST00000457717.6	TSL:5	c.1068-85C>T		intron	N/A	ENSP00000400821.1	P55157-1
	MTTP	ENST00000511045.6	TSL:2	c.819-85C>T		intron	N/A	ENSP00000427679.2	E9PBP6

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

African (AFR) AF: 0.0869 AC: 2454 AN: 28238

American (AMR) AF: 0.0739 AC: 3193 AN: 43192

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 6502 AN: 24356

East Asian (EAS) AF: 0.000340 AC: 13 AN: 38288

South Asian (SAS) AF: 0.0771 AC: 6111 AN: 79278

European-Finnish (FIN) AF: 0.0555 AC: 2701 AN: 48694

Middle Eastern (MID) AF: 0.186 AC: 785 AN: 4220

European-Non Finnish (NFE) AF: 0.121 AC: 109654 AN: 902966

Other (OTH) AF: 0.120 AC: 6280 AN: 52318

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

African (AFR) AF: 0.0857 AC: 3553 AN: 41442

American (AMR) AF: 0.107 AC: 1639 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 909 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5170

South Asian (SAS) AF: 0.0665 AC: 320 AN: 4814

European-Finnish (FIN) AF: 0.0547 AC: 577 AN: 10558

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8205 AN: 67932

Other (OTH) AF: 0.120 AC: 254 AN: 2110

Alfa AF: 0.108 Hom.: 129

Bravo AF: 0.107

Asia WGS AF: 0.0340 AC: 117 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.37
DANN	Benign	0.20
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17533517; hg19: chr4-100521637;