rs4374642

Positions:

• chr4-122179956-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384125.1(BLTP1):​c.358+4042T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 984,244 control chromosomes in the GnomAD database, including 5,104 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 0.13 (1717 hom., cov: 31)
  • Exomes 𝑓: 0.085 (3387 hom.)
• Consequence: BLTP1 NM_001384125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLTP1	NM_001384125.1	c.358+4042T>C		intron_variant		ENST00000679879.1	NP_001371054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLTP1	ENST00000679879.1	c.358+4042T>C		intron_variant			NM_001384125.1	ENSP00000505357	A2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19069 AN: 151100 Hom.: 1708 Cov.: 31

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0724

Gnomad ASJ AF: 0.0629

Gnomad EAS AF: 0.00253

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.0848 AC: 70682 AN: 833026 Hom.: 3387 Cov.: 28 AF XY: 0.0846 AC XY: 32544 AN XY: 384682

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.0569

Gnomad4 ASJ exome AF: 0.0732

Gnomad4 EAS exome AF: 0.00386

Gnomad4 SAS exome AF: 0.0647

Gnomad4 FIN exome AF: 0.0942

Gnomad4 NFE exome AF: 0.0818

Gnomad4 OTH exome AF: 0.0832

GnomAD4 genome AF: 0.126 AC: 19094 AN: 151218 Hom.: 1717 Cov.: 31 AF XY: 0.125 AC XY: 9250 AN XY: 73824

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.0723

Gnomad4 ASJ AF: 0.0629

Gnomad4 EAS AF: 0.00254

Gnomad4 SAS AF: 0.0646

Gnomad4 FIN AF: 0.0965

Gnomad4 NFE AF: 0.0821

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0883 Hom.: 487

Bravo AF: 0.129

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs4374642; hg19: chr4-123101111;