rs10516445

Variant names:

• chr4-99603522-C-G
• rs10516445
• NM_001386140.1:c.1344+1808C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-99603522-C-G
• chr4-99603522-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.1344+1808C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,830 control chromosomes in the GnomAD database, including 19,875 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 0.47 (19875 hom., cov: 31)
• Consequence: MTTP NM_001386140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTTP	NM_001386140.1	c.1344+1808C>G		intron_variant	Intron 10 of 17	ENST00000265517.10	NP_001373069.1
MTTP	NM_000253.4	c.1344+1808C>G		intron_variant	Intron 11 of 18		NP_000244.2
MTTP	NM_001300785.2	c.1095+1808C>G		intron_variant	Intron 10 of 17		NP_001287714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTTP	ENST00000265517.10	c.1344+1808C>G		intron_variant	Intron 10 of 17	1	NM_001386140.1	ENSP00000265517.5
MTTP	ENST00000457717.6	c.1344+1808C>G		intron_variant	Intron 11 of 18	5		ENSP00000400821.1
MTTP	ENST00000511045.6	c.1095+1808C>G		intron_variant	Intron 10 of 17	2		ENSP00000427679.2
ENSG00000248676	ENST00000508578.1	n.129-7881G>C		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71554 AN: 151712 Hom.: 19836 Cov.: 31

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.472 AC: 71635 AN: 151830 Hom.: 19875 Cov.: 31 AF XY: 0.466 AC XY: 34550 AN XY: 74208

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.461

Alfa AF: 0.396 Hom.: 1647

Bravo AF: 0.496

Asia WGS AF: 0.459 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.56

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: rs10516445; hg19: chr4-100524679;