rs1491246

Positions:

• chr4-99613325-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001386140.1(MTTP):​c.2217+185A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,180 control chromosomes in the GnomAD database, including 1,000 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (1000 hom., cov: 32)
• Consequence: MTTP NM_001386140.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0870

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 4-99613325-A-T is Benign according to our data. Variant chr4-99613325-A-T is described in ClinVar as [Benign]. Clinvar id is 1235879.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-99613325-A-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTTP	NM_001386140.1	c.2217+185A>T		intron_variant		ENST00000265517.10	NP_001373069.1
MTTP	NM_000253.4	c.2217+185A>T		intron_variant			NP_000244.2
MTTP	NM_001300785.2	c.1968+185A>T		intron_variant			NP_001287714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTTP	ENST00000265517.10	c.2217+185A>T		intron_variant		1	NM_001386140.1	ENSP00000265517	P1
	ENST00000508578.1	n.128+7562T>A		intron_variant, non_coding_transcript_variant		5
MTTP	ENST00000457717.6	c.2217+185A>T		intron_variant		5		ENSP00000400821	P1
MTTP	ENST00000511045.6	c.1968+185A>T		intron_variant		2		ENSP00000427679

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15864 AN: 152062 Hom.: 999 Cov.: 32

Gnomad AFR AF: 0.0861

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0666

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.104 AC: 15884 AN: 152180 Hom.: 1000 Cov.: 32 AF XY: 0.103 AC XY: 7632 AN XY: 74402

Gnomad4 AFR AF: 0.0865

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0667

Gnomad4 FIN AF: 0.0547

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.120

Alfa AF: 0.113 Hom.: 129

Bravo AF: 0.107

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.6
DANN	Benign	0.78

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: rs1491246; hg19: chr4-100534482;