4-122239668-A-T

Variant names:

• chr4-122239668-A-T
• rs770791100
• NM_001384125.1:c.3986A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 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. 14/22 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. Y1329C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BLTP1 NM_001384125.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.29
• Publications: 0 publications found

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]

BLTP1 Gene-Disease associations (from GenCC):

• Alkuraya-Kucinskas syndrome

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08657402).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384125.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP1	NM_001384125.1	MANE Select	c.3986A>T	p.Tyr1329Phe	missense	Exon 29 of 88	NP_001371054.1
	BLTP1	NM_015312.4		c.3986A>T	p.Tyr1329Phe	missense	Exon 27 of 84	NP_056127.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP1	ENST00000679879.1	MANE Select	c.3986A>T	p.Tyr1329Phe	missense	Exon 29 of 88	ENSP00000505357.1
	BLTP1	ENST00000388738.8	TSL:1	c.3986A>T	p.Tyr1329Phe	missense	Exon 29 of 85	ENSP00000373390.4
	BLTP1	ENST00000264501.8	TSL:5	c.3986A>T	p.Tyr1329Phe	missense	Exon 29 of 86	ENSP00000264501.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		6.3
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.090
Sift	Benign	0.30	T
Sift4G	Benign	0.94	T
Polyphen		0.0020	B
Vest4		0.22
MutPred		0.28		Loss of sheet (P = 0.0181)
MVP		0.30
MPC		0.11
ClinPred		0.44	T
GERP RS		6.0
PromoterAI		0.026	Neutral
Varity_R		0.13
gMVP		0.29
Mutation Taster		=47/53	disease causing

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: rs770791100; hg19: chr4-123160823; COSMIC: COSV52695429; COSMIC: COSV52695429;