4-122277280-A-G

Variant names:

• chr4-122277280-A-G
• rs6534347
• NM_001384125.1:c.8591+1258A>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.8591+1258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,064 control chromosomes in the GnomAD database, including 29,942 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 0.62 (29942 hom., cov: 31)
• Consequence: BLTP1 NM_001384125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 27 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.664 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.8591+1258A>G		intron	N/A	NP_001371054.1
	BLTP1	NM_015312.4		c.8591+1258A>G		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.8591+1258A>G		intron	N/A	ENSP00000505357.1
	BLTP1	ENST00000388738.8	TSL:1	c.8541-2495A>G		intron	N/A	ENSP00000373390.4
	BLTP1	ENST00000419325.5	TSL:1	c.2462+1258A>G		intron	N/A	ENSP00000393219.1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94781 AN: 151946 Hom.: 29911 Cov.: 31

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.624 AC: 94871 AN: 152064 Hom.: 29942 Cov.: 31 AF XY: 0.619 AC XY: 45978 AN XY: 74330

African (AFR) AF: 0.671 AC: 27821 AN: 41472

American (AMR) AF: 0.555 AC: 8473 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2546 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2130 AN: 5162

South Asian (SAS) AF: 0.672 AC: 3240 AN: 4820

European-Finnish (FIN) AF: 0.521 AC: 5502 AN: 10568

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42868 AN: 67980

Other (OTH) AF: 0.660 AC: 1396 AN: 2114

Alfa AF: 0.624 Hom.: 3857

Bravo AF: 0.626

Asia WGS AF: 0.576 AC: 2008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.51
PhyloP100		-0.50
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: rs6534347; hg19: chr4-123198435;