4-122319464-G-A

Variant names:

• chr4-122319464-G-A
• rs13152362
• NM_001384125.1:c.10995+1194G>A

Variant summary

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

The NM_001384125.1(BLTP1):​c.10995+1194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 149,322 control chromosomes in the GnomAD database, including 3,841 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 0.22 (3841 hom., cov: 31)
• Consequence: BLTP1 NM_001384125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 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.10995+1194G>A		intron	N/A	NP_001371054.1
	BLTP1	NM_015312.4		c.10794+1194G>A		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.10995+1194G>A		intron	N/A	ENSP00000505357.1
	BLTP1	ENST00000388738.8	TSL:1	c.10743+1194G>A		intron	N/A	ENSP00000373390.4
	BLTP1	ENST00000419325.5	TSL:1	c.4665+1194G>A		intron	N/A	ENSP00000393219.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 32801 AN: 149246 Hom.: 3842 Cov.: 31

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0478

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.173

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.220 AC: 32808 AN: 149322 Hom.: 3841 Cov.: 31 AF XY: 0.212 AC XY: 15432 AN XY: 72730

African (AFR) AF: 0.287 AC: 11708 AN: 40784

American (AMR) AF: 0.160 AC: 2398 AN: 15020

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 760 AN: 3448

East Asian (EAS) AF: 0.0473 AC: 240 AN: 5070

South Asian (SAS) AF: 0.172 AC: 810 AN: 4718

European-Finnish (FIN) AF: 0.132 AC: 1277 AN: 9682

Middle Eastern (MID) AF: 0.176 AC: 51 AN: 290

European-Non Finnish (NFE) AF: 0.222 AC: 14913 AN: 67320

Other (OTH) AF: 0.222 AC: 461 AN: 2080

Alfa AF: 0.191 Hom.: 646

Bravo AF: 0.220

Asia WGS AF: 0.126 AC: 437 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.17
PhyloP100		-1.7
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: rs13152362; hg19: chr4-123240619;