4-122361617-G-T

Variant names:

• chr4-122361617-G-T
• rs7678445
• NM_001384125.1:c.15066-414G>T

Variant summary

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

The NM_001384125.1(BLTP1):​c.15066-414G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0491 in 152,080 control chromosomes in the GnomAD database, including 258 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 0.049 (258 hom., cov: 32)
• Consequence: BLTP1 NM_001384125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 9 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: Genomics England PanelApp, G2P, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000310421 (HGNC:58882):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0722 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP1	NM_001384125.1	MANE Select	c.15066-414G>T		intron	N/A	NP_001371054.1	A0A7P0T938
	BLTP1	NM_015312.4		c.14802-414G>T		intron	N/A	NP_056127.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP1	ENST00000679879.1	MANE Select	c.15066-414G>T		intron	N/A	ENSP00000505357.1	A0A7P0T938
	BLTP1	ENST00000388738.8	TSL:1	c.14457-414G>T		intron	N/A	ENSP00000373390.4	A0A8J8Z0T9
	BLTP1	ENST00000306802.8	TSL:1	c.3927-414G>T		intron	N/A	ENSP00000304374.4	H3BLT5

Frequencies

GnomAD3 genomes AF: 0.0492 AC: 7472 AN: 151962 Hom.: 258 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0952

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0739

Gnomad OTH AF: 0.0441

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

GnomAD4 genome AF: 0.0491 AC: 7464 AN: 152080 Hom.: 258 Cov.: 32 AF XY: 0.0498 AC XY: 3700 AN XY: 74332

African (AFR) AF: 0.0103 AC: 428 AN: 41526

American (AMR) AF: 0.0379 AC: 579 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.0315 AC: 152 AN: 4826

European-Finnish (FIN) AF: 0.0952 AC: 1002 AN: 10524

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0739 AC: 5020 AN: 67952

Other (OTH) AF: 0.0427 AC: 90 AN: 2108

Alfa AF: 0.0625 Hom.: 231

Bravo AF: 0.0426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.55
PhyloP100		0.18
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: rs7678445; hg19: chr4-123282772;