rs79194015

Positions:

• chr4-99597326-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.1067+102A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,276,698 control chromosomes in the GnomAD database, including 8,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1003 hom., cov: 32)
  • Exomes 𝑓: 0.11 (7649 hom.)
• Consequence: MTTP NM_001386140.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.331

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=-0.92).
• BP6: Variant 4-99597326-A-T is Benign according to our data. Variant chr4-99597326-A-T is described in ClinVar as [Benign]. Clinvar id is 1295323.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-99597326-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	UniProt
MTTP	NM_001386140.1	c.1067+102A>T		intron_variant		ENST00000265517.10
MTTP	NM_000253.4	c.1067+102A>T		intron_variant
MTTP	NM_001300785.2	c.818+102A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTTP	ENST00000265517.10	c.1067+102A>T		intron_variant		1	NM_001386140.1	P1
	ENST00000508578.1	n.129-1685T>A		intron_variant, non_coding_transcript_variant		5
MTTP	ENST00000457717.6	c.1067+102A>T		intron_variant		5		P1
MTTP	ENST00000511045.6	c.818+102A>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15869 AN: 152124 Hom.: 1002 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: 0.000577

Gnomad SAS AF: 0.0668

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.108 AC: 121765 AN: 1124456 Hom.: 7649 AF XY: 0.108 AC XY: 61875 AN XY: 572582

Gnomad4 AFR exome AF: 0.0845

Gnomad4 AMR exome AF: 0.0744

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.000325

Gnomad4 SAS exome AF: 0.0764

Gnomad4 FIN exome AF: 0.0563

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.104 AC: 15889 AN: 152242 Hom.: 1003 Cov.: 32 AF XY: 0.103 AC XY: 7641 AN XY: 74450

Gnomad4 AFR AF: 0.0864

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0669

Gnomad4 FIN AF: 0.0547

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.121

Alfa AF: 0.113 Hom.: 129

Bravo AF: 0.108

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

Apr 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.9
DANN	Benign	0.68

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: rs79194015; hg19: chr4-100518483;