rs1800804

Variant names:

• chr4-99574660-T-C
• rs1800804
• NM_000253.4:c.-101-149T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-99574660-T-C
• chr4-99574660-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000253.4(MTTP):​c.-101-149T>C 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 756,350 control chromosomes in the GnomAD database, including 27,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5371 hom., cov: 32)
  • Exomes 𝑓: 0.26 (21840 hom.)
• Consequence: MTTP NM_000253.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.766
• Publications: 24 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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-99574660-T-C is Benign according to our data. Variant chr4-99574660-T-C is described in ClinVar as Benign. ClinVar VariationId is 1168853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 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_000253.4		c.-101-149T>C		intron	N/A	NP_000244.2	P55157-1
	MTTP	NM_001300785.2		c.-188-7245T>C		intron	N/A	NP_001287714.2	E9PBP6
	MTTP	NM_001386140.1	MANE Select	c.-250T>C		upstream_gene	N/A	NP_001373069.1	P55157-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTTP	ENST00000457717.6	TSL:5	c.-101-149T>C		intron	N/A	ENSP00000400821.1	P55157-1
	MTTP	ENST00000511045.6	TSL:2	c.-188-7245T>C		intron	N/A	ENSP00000427679.2	E9PBP6
	MTTP	ENST00000511610.6	TSL:4	c.-101-149T>C		intron	N/A	ENSP00000422178.2	D6R915

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39787 AN: 151934 Hom.: 5363 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.263 AC: 158707 AN: 604296 Hom.: 21840 Cov.: 8 AF XY: 0.267 AC XY: 84983 AN XY: 318270

African (AFR) AF: 0.290 AC: 4449 AN: 15332

American (AMR) AF: 0.180 AC: 4778 AN: 26554

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 6662 AN: 16750

East Asian (EAS) AF: 0.152 AC: 4407 AN: 28986

South Asian (SAS) AF: 0.340 AC: 19289 AN: 56786

European-Finnish (FIN) AF: 0.191 AC: 5404 AN: 28336

Middle Eastern (MID) AF: 0.340 AC: 1015 AN: 2988

European-Non Finnish (NFE) AF: 0.262 AC: 104275 AN: 397886

Other (OTH) AF: 0.275 AC: 8428 AN: 30678

GnomAD4 genome AF: 0.262 AC: 39818 AN: 152054 Hom.: 5371 Cov.: 32 AF XY: 0.260 AC XY: 19353 AN XY: 74302

African (AFR) AF: 0.278 AC: 11504 AN: 41446

American (AMR) AF: 0.237 AC: 3627 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1384 AN: 3466

East Asian (EAS) AF: 0.146 AC: 754 AN: 5176

South Asian (SAS) AF: 0.347 AC: 1672 AN: 4816

European-Finnish (FIN) AF: 0.190 AC: 2012 AN: 10576

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17695 AN: 67974

Other (OTH) AF: 0.297 AC: 626 AN: 2108

Alfa AF: 0.264 Hom.: 7468

Bravo AF: 0.261

Asia WGS AF: 0.290 AC: 1007 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.34
DANN	Benign	0.36
PhyloP100		-0.77
PromoterAI		-0.028	Neutral
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: rs1800804; hg19: chr4-100495817;