4-122239668-A-T

Variant names:

• chr4-122239668-A-T
• NM_001384125.1:c.3986A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_001384125.1(BLTP1):​c.3986A>T​(p.Tyr1329Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y1329S) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BLTP1 NM_001384125.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.29

Genes affected

BLTP1 (HGNC:26953): (bridge-like lipid transfer protein family member 1) This gene is located on the long arm of chromosome 4 in a region that is associated with susceptibility to celiac disease. The encoded protein is similar to a Chinese hamster protein that is associated with spermatocyte and adipocyte differentiation. The C-terminus of the protein is also similar to a Caenorhabditis elegans protein that plays a role in lipid storage. In mammals, this protein is thought to function in the regulation of epithelial growth and differentiation, and in tumor development. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr4-122239668-A-C is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.08657402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLTP1	NM_001384125.1	c.3986A>T	p.Tyr1329Phe	missense_variant	Exon 29 of 88	ENST00000679879.1	NP_001371054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLTP1	ENST00000679879.1	c.3986A>T	p.Tyr1329Phe	missense_variant	Exon 29 of 88		NM_001384125.1	ENSP00000505357.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.0086	T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	.;D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.090
Sift	Benign	0.30	T;T
Sift4G	Benign	0.94	T;T
Polyphen		0.0020	B;B
Vest4		0.22
MutPred		0.28		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.30
MPC		0.11
ClinPred		0.44	T
GERP RS		6.0
Varity_R		0.13
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-123160823; COSMIC: COSV52695429; COSMIC: COSV52695429;