4-122342291-T-C

Variant names:

• chr4-122342291-T-C
• rs6851362
• NM_001384125.1:c.12617-1119T>C

Variant summary

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

The NM_001384125.1(BLTP1):​c.12617-1119T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,906 control chromosomes in the GnomAD database, including 4,883 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 0.24 (4883 hom., cov: 32)
• Consequence: BLTP1 NM_001384125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.868
• Publications: 11 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

ENSG00000310421 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP1	NM_001384125.1	MANE Select	c.12617-1119T>C		intron	N/A	NP_001371054.1
	BLTP1	NM_015312.4		c.12353-1119T>C		intron	N/A	NP_056127.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP1	ENST00000679879.1	MANE Select	c.12617-1119T>C		intron	N/A	ENSP00000505357.1
	BLTP1	ENST00000388738.8	TSL:1	c.12260-1119T>C		intron	N/A	ENSP00000373390.4
	BLTP1	ENST00000306802.8	TSL:1	c.1478-1119T>C		intron	N/A	ENSP00000304374.4

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36917 AN: 151788 Hom.: 4884 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.0457

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.243 AC: 36936 AN: 151906 Hom.: 4883 Cov.: 32 AF XY: 0.233 AC XY: 17291 AN XY: 74256

African (AFR) AF: 0.315 AC: 13038 AN: 41386

American (AMR) AF: 0.188 AC: 2867 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 877 AN: 3468

East Asian (EAS) AF: 0.0452 AC: 234 AN: 5176

South Asian (SAS) AF: 0.135 AC: 648 AN: 4802

European-Finnish (FIN) AF: 0.130 AC: 1370 AN: 10558

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17001 AN: 67944

Other (OTH) AF: 0.253 AC: 532 AN: 2106

Alfa AF: 0.239 Hom.: 2791

Bravo AF: 0.252

Asia WGS AF: 0.123 AC: 428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.28
PhyloP100		-0.87
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: rs6851362; hg19: chr4-123263446;