rs7693203

chr4-99578973-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386140.1(MTTP):c.62-2932C>T 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 152,042 control chromosomes in the GnomAD database, including 5,392 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 (5392 hom., cov: 32)
• Consequence: MTTP NM_001386140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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/exons	MANE	UniProt
MTTP	NM_001386140.1	c.62-2932C>T		intron_variant		ENST00000265517.10
MTTP	NM_000253.4	c.62-2932C>T		intron_variant
MTTP	NM_001300785.2	c.-188-2932C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTTP	ENST00000265517.10	c.62-2932C>T		intron_variant		1	NM_001386140.1	P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39829 AN: 151924 Hom.: 5384 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.260

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: 39860 AN: 152042 Hom.: 5392 Cov.: 32 AF XY: 0.261 AC XY: 19396 AN XY: 74340

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.298

Alfa AF: 0.266 Hom.: 2651

Bravo AF: 0.261

Asia WGS AF: 0.290 AC: 1007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.7
Dann	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs7693203; hg19: chr4-100500130;