rs79194015

Variant names:

• chr4-99597326-A-T
• rs79194015
• NM_001386140.1:c.1067+102A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.331
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, PanelApp Australia, G2P

ENSG00000248676 (HGNC:54189):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1295323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386140.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTTP	NM_001386140.1	MANE Select	c.1067+102A>T		intron	N/A	NP_001373069.1
	MTTP	NM_000253.4		c.1067+102A>T		intron	N/A	NP_000244.2
	MTTP	NM_001300785.2		c.818+102A>T		intron	N/A	NP_001287714.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTTP	ENST00000265517.10	TSL:1 MANE Select	c.1067+102A>T		intron	N/A	ENSP00000265517.5
	MTTP	ENST00000457717.6	TSL:5	c.1067+102A>T		intron	N/A	ENSP00000400821.1
	MTTP	ENST00000511045.6	TSL:2	c.818+102A>T		intron	N/A	ENSP00000427679.2

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

African (AFR) AF: 0.0845 AC: 2245 AN: 26556

American (AMR) AF: 0.0744 AC: 3078 AN: 41358

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 6163 AN: 23302

East Asian (EAS) AF: 0.000325 AC: 12 AN: 36902

South Asian (SAS) AF: 0.0764 AC: 5932 AN: 77634

European-Finnish (FIN) AF: 0.0563 AC: 2138 AN: 37988

Middle Eastern (MID) AF: 0.184 AC: 907 AN: 4918

European-Non Finnish (NFE) AF: 0.116 AC: 95529 AN: 826744

Other (OTH) AF: 0.117 AC: 5761 AN: 49054

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

African (AFR) AF: 0.0864 AC: 3589 AN: 41528

American (AMR) AF: 0.108 AC: 1647 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 908 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0669 AC: 323 AN: 4830

European-Finnish (FIN) AF: 0.0547 AC: 581 AN: 10622

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8214 AN: 68002

Other (OTH) AF: 0.121 AC: 255 AN: 2116

Alfa AF: 0.113 Hom.: 129

Bravo AF: 0.108

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.9
DANN	Benign	0.68
PhyloP100		0.33
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: rs79194015; hg19: chr4-100518483;