12-109875949-T-C

Variant names:

• chr12-109875949-T-C
• rs4766642
• NM_016433.4:c.103+4323A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016433.4(GLTP):​c.103+4323A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,138 control chromosomes in the GnomAD database, including 32,366 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 0.64 (32366 hom., cov: 33)
• Consequence: GLTP NM_016433.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 3 publications found

Genes affected

GLTP (HGNC:24867): (glycolipid transfer protein) The protein encoded by this gene is similar to bovine and porcine proteins which accelerate transfer of certain glycosphingolipids and glyceroglycolipids between membranes. It is thought to be a cytoplasmic protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016433.4. 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
	GLTP	NM_016433.4	MANE Select	c.103+4323A>G		intron	N/A	NP_057517.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLTP	ENST00000318348.9	TSL:1 MANE Select	c.103+4323A>G		intron	N/A	ENSP00000315263.3
	GLTP	ENST00000544393.5	TSL:3	c.103+4323A>G		intron	N/A	ENSP00000445919.1
	GLTP	ENST00000540772.1	TSL:5	c.53+4323A>G		intron	N/A	ENSP00000440136.1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97824 AN: 152020 Hom.: 32318 Cov.: 33

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.644 AC: 97932 AN: 152138 Hom.: 32366 Cov.: 33 AF XY: 0.646 AC XY: 48032 AN XY: 74360

African (AFR) AF: 0.760 AC: 31553 AN: 41502

American (AMR) AF: 0.691 AC: 10560 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1813 AN: 3472

East Asian (EAS) AF: 0.352 AC: 1825 AN: 5188

South Asian (SAS) AF: 0.710 AC: 3426 AN: 4826

European-Finnish (FIN) AF: 0.663 AC: 7006 AN: 10570

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39844 AN: 67974

Other (OTH) AF: 0.622 AC: 1313 AN: 2110

Alfa AF: 0.617 Hom.: 6731

Bravo AF: 0.644

Asia WGS AF: 0.605 AC: 2103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.71
PhyloP100		-2.1
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: rs4766642; hg19: chr12-110313754;