4-122175683-C-T

Variant names:

• chr4-122175683-C-T
• rs28602944
• NM_001384125.1:c.294-167C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001384125.1(BLTP1):​c.294-167C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 155,292 control chromosomes in the GnomAD database, including 885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.064 (884 hom., cov: 32)
  • Exomes 𝑓: 0.011 (1 hom.)
• Consequence: BLTP1 NM_001384125.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.375
• Publications: 1 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 4-122175683-C-T is Benign according to our data. Variant chr4-122175683-C-T is described in ClinVar as Benign. ClinVar VariationId is 1294831.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 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.294-167C>T		intron	N/A	NP_001371054.1	A0A7P0T938
	BLTP1	NM_015312.4		c.294-167C>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.294-167C>T		intron	N/A	ENSP00000505357.1	A0A7P0T938
	BLTP1	ENST00000388738.8	TSL:1	c.294-167C>T		intron	N/A	ENSP00000373390.4	A0A8J8Z0T9
	BLTP1	ENST00000264501.8	TSL:5	c.294-167C>T		intron	N/A	ENSP00000264501.4	Q2LD37-1

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9741 AN: 152012 Hom.: 880 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00747

Gnomad OTH AF: 0.0550

GnomAD4 exome AF: 0.0114 AC: 36 AN: 3162 Hom.: 1 AF XY: 0.0105 AC XY: 16 AN XY: 1530

African (AFR) AF: 0.156 AC: 10 AN: 64

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 1 AN: 22

East Asian (EAS) AF: 0.00 AC: 0 AN: 8

South Asian (SAS) AF: 0.0536 AC: 3 AN: 56

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.00687 AC: 20 AN: 2910

Other (OTH) AF: 0.0217 AC: 2 AN: 92

GnomAD4 genome AF: 0.0642 AC: 9766 AN: 152130 Hom.: 884 Cov.: 32 AF XY: 0.0628 AC XY: 4671 AN XY: 74378

African (AFR) AF: 0.205 AC: 8490 AN: 41466

American (AMR) AF: 0.0271 AC: 414 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3466

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.0313 AC: 151 AN: 4826

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10598

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00747 AC: 508 AN: 67988

Other (OTH) AF: 0.0545 AC: 115 AN: 2112

Alfa AF: 0.0457 Hom.: 107

Bravo AF: 0.0720

Asia WGS AF: 0.0280 AC: 98 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.47
PhyloP100		-0.38
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: rs28602944; hg19: chr4-123096838;