rs2866164

Variant names:

• chr4-99569786-C-G
• rs2866164
• NM_000253.4:c.-101-5023C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-99569786-C-G
• chr4-99569786-C-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.-101-5023C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 151,754 control chromosomes in the GnomAD database, including 5,375 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 0.26 (5375 hom., cov: 32)
• Consequence: MTTP NM_000253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• Publications: 80 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTTP	NM_000253.4	c.-101-5023C>G		intron_variant	Intron 1 of 18		NP_000244.2
MTTP	NM_001300785.2	c.-189+5549C>G		intron_variant	Intron 1 of 17		NP_001287714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTTP	ENST00000457717.6	c.-101-5023C>G		intron_variant	Intron 1 of 18	5		ENSP00000400821.1
MTTP	ENST00000511045.6	c.-189+5549C>G		intron_variant	Intron 1 of 17	2		ENSP00000427679.2
MTTP	ENST00000511610.6	c.-267-914C>G		intron_variant	Intron 1 of 3	4		ENSP00000422178.2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39744 AN: 151634 Hom.: 5367 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.262 AC: 39775 AN: 151754 Hom.: 5375 Cov.: 32 AF XY: 0.261 AC XY: 19341 AN XY: 74152

African (AFR) AF: 0.278 AC: 11507 AN: 41444

American (AMR) AF: 0.238 AC: 3622 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1383 AN: 3468

East Asian (EAS) AF: 0.147 AC: 762 AN: 5168

South Asian (SAS) AF: 0.347 AC: 1673 AN: 4820

European-Finnish (FIN) AF: 0.190 AC: 2010 AN: 10566

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.261 AC: 17645 AN: 67726

Other (OTH) AF: 0.298 AC: 629 AN: 2110

Alfa AF: 0.255 Hom.: 660

Bravo AF: 0.261

Asia WGS AF: 0.288 AC: 994 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.60
PhyloP100		-0.39
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: rs2866164; hg19: chr4-100490943;