rs7698798

Variant names:

• chr4-99608119-A-C
• rs7698798
• NM_001386140.1:c.1558-647A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-99608119-A-C
• chr4-99608119-A-G
• chr4-99608119-A-T

Variant summary

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

The NM_000253.4(MTTP):​c.1558-647A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,078 control chromosomes in the GnomAD database, including 19,898 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 (19898 hom., cov: 32)
• Consequence: MTTP NM_000253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.952
• Publications: 2 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:54189):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• 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_000253.4. 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.1558-647A>C		intron	N/A	NP_001373069.1
	MTTP	NM_000253.4		c.1558-647A>C		intron	N/A	NP_000244.2
	MTTP	NM_001300785.2		c.1309-647A>C		intron	N/A	NP_001287714.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTTP	ENST00000265517.10	TSL:1 MANE Select	c.1558-647A>C		intron	N/A	ENSP00000265517.5
	MTTP	ENST00000457717.6	TSL:5	c.1558-647A>C		intron	N/A	ENSP00000400821.1
	MTTP	ENST00000511045.6	TSL:2	c.1309-647A>C		intron	N/A	ENSP00000427679.2

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71615 AN: 151960 Hom.: 19857 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.516

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: 0.471 AC: 71699 AN: 152078 Hom.: 19898 Cov.: 32 AF XY: 0.465 AC XY: 34586 AN XY: 74358

African (AFR) AF: 0.755 AC: 31324 AN: 41478

American (AMR) AF: 0.365 AC: 5583 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1993 AN: 3472

East Asian (EAS) AF: 0.629 AC: 3248 AN: 5162

South Asian (SAS) AF: 0.413 AC: 1987 AN: 4812

European-Finnish (FIN) AF: 0.206 AC: 2182 AN: 10604

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.351 AC: 23835 AN: 67956

Other (OTH) AF: 0.461 AC: 972 AN: 2110

Alfa AF: 0.410 Hom.: 2287

Bravo AF: 0.496

Asia WGS AF: 0.458 AC: 1595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.3
DANN	Benign	0.41
PhyloP100		0.95
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: rs7698798; hg19: chr4-100529276;