rs4374642

Variant names:

• chr4-122179956-T-C
• rs4374642
• NM_001384125.1:c.358+4042T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-122179956-T-C
• chr4-122179956-T-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.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
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 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.358+4042T>C		intron	N/A	NP_001371054.1
	BLTP1	NM_015312.4		c.358+4042T>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.358+4042T>C		intron	N/A	ENSP00000505357.1
	BLTP1	ENST00000388738.8	TSL:1	c.358+4042T>C		intron	N/A	ENSP00000373390.4
	BLTP1	ENST00000264501.8	TSL:5	c.358+4042T>C		intron	N/A	ENSP00000264501.4

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

African (AFR) AF: 0.277 AC: 4371 AN: 15784

American (AMR) AF: 0.0569 AC: 56 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 377 AN: 5152

East Asian (EAS) AF: 0.00386 AC: 14 AN: 3630

South Asian (SAS) AF: 0.0647 AC: 1065 AN: 16458

European-Finnish (FIN) AF: 0.0942 AC: 26 AN: 276

Middle Eastern (MID) AF: 0.0988 AC: 160 AN: 1620

European-Non Finnish (NFE) AF: 0.0818 AC: 62342 AN: 761830

Other (OTH) AF: 0.0832 AC: 2271 AN: 27292

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

African (AFR) AF: 0.258 AC: 10587 AN: 41086

American (AMR) AF: 0.0723 AC: 1094 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 218 AN: 3468

East Asian (EAS) AF: 0.00254 AC: 13 AN: 5124

South Asian (SAS) AF: 0.0646 AC: 310 AN: 4802

European-Finnish (FIN) AF: 0.0965 AC: 1003 AN: 10390

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.0821 AC: 5575 AN: 67904

Other (OTH) AF: 0.108 AC: 227 AN: 2102

Alfa AF: 0.0921 Hom.: 595

Bravo AF: 0.129

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.7
DANN	Benign	0.76
PhyloP100		-0.23
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: rs4374642; hg19: chr4-123101111;