4-99622147-T-G

Position:

• chr4-99622147-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000248676 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTTP	NM_001386140.1	c.2514-530T>G		intron_variant		ENST00000265517.10	NP_001373069.1
MTTP	NM_000253.4	c.2514-530T>G		intron_variant			NP_000244.2
MTTP	NM_001300785.2	c.2265-530T>G		intron_variant			NP_001287714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTTP	ENST00000265517.10	c.2514-530T>G		intron_variant		1	NM_001386140.1	ENSP00000265517.5
MTTP	ENST00000457717.6	c.2514-530T>G		intron_variant		5		ENSP00000400821.1
MTTP	ENST00000511045.6	c.2265-530T>G		intron_variant		2		ENSP00000427679.2
ENSG00000248676	ENST00000508578.1	n.33-1165A>C		intron_variant		5

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

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.0534

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.148

Alfa AF: 0.138 Hom.: 3257

Bravo AF: 0.153

Asia WGS AF: 0.216 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.60

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: rs881980; hg19: chr4-100543304;