4-99622147-T-G

Variant names:

• chr4-99622147-T-G
• rs881980
• NM_001386140.1:c.2514-530T>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.2514-530T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,246 control chromosomes in the GnomAD database, including 2,042 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 0.15 (2042 hom., cov: 32)
• Consequence: MTTP NM_001386140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 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.2514-530T>G		intron	N/A	NP_001373069.1	P55157-1
	MTTP	NM_000253.4		c.2514-530T>G		intron	N/A	NP_000244.2	P55157-1
	MTTP	NM_001300785.2		c.2265-530T>G		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.2514-530T>G		intron	N/A	ENSP00000265517.5	P55157-1
	MTTP	ENST00000457717.6	TSL:5	c.2514-530T>G		intron	N/A	ENSP00000400821.1	P55157-1
	MTTP	ENST00000511045.6	TSL:2	c.2265-530T>G		intron	N/A	ENSP00000427679.2	E9PBP6

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22344 AN: 152128 Hom.: 2044 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0534

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.147 AC: 22339 AN: 152246 Hom.: 2042 Cov.: 32 AF XY: 0.146 AC XY: 10838 AN XY: 74440

African (AFR) AF: 0.169 AC: 7026 AN: 41540

American (AMR) AF: 0.108 AC: 1654 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 705 AN: 3472

East Asian (EAS) AF: 0.437 AC: 2262 AN: 5172

South Asian (SAS) AF: 0.192 AC: 927 AN: 4818

European-Finnish (FIN) AF: 0.0534 AC: 567 AN: 10616

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8750 AN: 68014

Other (OTH) AF: 0.148 AC: 312 AN: 2114

Alfa AF: 0.139 Hom.: 5035

Bravo AF: 0.153

Asia WGS AF: 0.216 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.60
PhyloP100		-0.22
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: rs881980; hg19: chr4-100543304;