chr4-99603522-C-G

Variant names:

• chr4-99603522-C-G
• rs10516445
• NM_001386140.1:c.1344+1808C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386140.1(MTTP):​c.1344+1808C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,830 control chromosomes in the GnomAD database, including 19,875 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (19875 hom., cov: 31)
• Consequence: MTTP NM_001386140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 5 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, PanelApp Australia, G2P

ENSG00000248676 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTTP	NM_001386140.1	MANE Select	c.1344+1808C>G		intron	N/A	NP_001373069.1
	MTTP	NM_000253.4		c.1344+1808C>G		intron	N/A	NP_000244.2
	MTTP	NM_001300785.2		c.1095+1808C>G		intron	N/A	NP_001287714.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTTP	ENST00000265517.10	TSL:1 MANE Select	c.1344+1808C>G		intron	N/A	ENSP00000265517.5
	MTTP	ENST00000457717.6	TSL:5	c.1344+1808C>G		intron	N/A	ENSP00000400821.1
	MTTP	ENST00000511045.6	TSL:2	c.1095+1808C>G		intron	N/A	ENSP00000427679.2

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71554 AN: 151712 Hom.: 19836 Cov.: 31

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.458

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.472 AC: 71635 AN: 151830 Hom.: 19875 Cov.: 31 AF XY: 0.466 AC XY: 34550 AN XY: 74208

African (AFR) AF: 0.755 AC: 31290 AN: 41430

American (AMR) AF: 0.365 AC: 5563 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1992 AN: 3470

East Asian (EAS) AF: 0.630 AC: 3246 AN: 5156

South Asian (SAS) AF: 0.414 AC: 1991 AN: 4810

European-Finnish (FIN) AF: 0.206 AC: 2166 AN: 10536

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23832 AN: 67880

Other (OTH) AF: 0.461 AC: 975 AN: 2114

Alfa AF: 0.396 Hom.: 1647

Bravo AF: 0.496

Asia WGS AF: 0.459 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.56
PhyloP100		0.21
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: rs10516445; hg19: chr4-100524679;