rs4505848

Variant names:

• chr4-122211337-A-G
• rs4505848
• NM_001384125.1:c.2247+242A>G

Variant summary

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

The NM_001384125.1(BLTP1):​c.2247+242A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 150,584 control chromosomes in the GnomAD database, including 7,527 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 0.29 (7527 hom., cov: 32)
• Consequence: BLTP1 NM_001384125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 67 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLTP1	NM_001384125.1	c.2247+242A>G		intron_variant	Intron 20 of 87	ENST00000679879.1	NP_001371054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLTP1	ENST00000679879.1	c.2247+242A>G		intron_variant	Intron 20 of 87		NM_001384125.1	ENSP00000505357.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44239 AN: 150468 Hom.: 7527 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.294 AC: 44246 AN: 150584 Hom.: 7527 Cov.: 32 AF XY: 0.301 AC XY: 22142 AN XY: 73592

African (AFR) AF: 0.121 AC: 4979 AN: 41034

American (AMR) AF: 0.404 AC: 6118 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 752 AN: 3432

East Asian (EAS) AF: 0.449 AC: 2315 AN: 5158

South Asian (SAS) AF: 0.286 AC: 1335 AN: 4664

European-Finnish (FIN) AF: 0.469 AC: 4933 AN: 10526

Middle Eastern (MID) AF: 0.188 AC: 54 AN: 288

European-Non Finnish (NFE) AF: 0.342 AC: 23000 AN: 67348

Other (OTH) AF: 0.278 AC: 578 AN: 2076

Alfa AF: 0.325 Hom.: 30061

Bravo AF: 0.280

Asia WGS AF: 0.300 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.72
PhyloP100		-0.089
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: rs4505848; hg19: chr4-123132492;