chr4-122343330-T-C

Variant names:

• chr4-122343330-T-C
• rs7699742
• NM_001384125.1:c.12617-80T>C

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.12617-80T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,551,920 control chromosomes in the GnomAD database, including 89,729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7533 hom., cov: 32)
  • Exomes 𝑓: 0.33 (82196 hom.)
• Consequence: BLTP1 NM_001384125.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.456
• Publications: 11 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

ENSG00000310421 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-122343330-T-C is Benign according to our data. Variant chr4-122343330-T-C is described in ClinVar as Benign. ClinVar VariationId is 1222692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 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.12617-80T>C		intron	N/A	NP_001371054.1
	BLTP1	NM_015312.4		c.12353-80T>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.12617-80T>C		intron	N/A	ENSP00000505357.1
	BLTP1	ENST00000388738.8	TSL:1	c.12260-80T>C		intron	N/A	ENSP00000373390.4
	BLTP1	ENST00000306802.8	TSL:1	c.1478-80T>C		intron	N/A	ENSP00000304374.4

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44254 AN: 152016 Hom.: 7533 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.274

GnomAD4 exome AF: 0.335 AC: 468436 AN: 1399786 Hom.: 82196 Cov.: 28 AF XY: 0.332 AC XY: 229365 AN XY: 691398

African (AFR) AF: 0.103 AC: 3311 AN: 32010

American (AMR) AF: 0.490 AC: 19050 AN: 38898

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 5307 AN: 24068

East Asian (EAS) AF: 0.469 AC: 18186 AN: 38804

South Asian (SAS) AF: 0.271 AC: 21754 AN: 80168

European-Finnish (FIN) AF: 0.470 AC: 23253 AN: 49508

Middle Eastern (MID) AF: 0.181 AC: 714 AN: 3936

European-Non Finnish (NFE) AF: 0.335 AC: 359514 AN: 1074540

Other (OTH) AF: 0.300 AC: 17347 AN: 57854

GnomAD4 genome AF: 0.291 AC: 44259 AN: 152134 Hom.: 7533 Cov.: 32 AF XY: 0.298 AC XY: 22149 AN XY: 74356

African (AFR) AF: 0.121 AC: 5031 AN: 41542

American (AMR) AF: 0.398 AC: 6084 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3466

East Asian (EAS) AF: 0.446 AC: 2303 AN: 5166

South Asian (SAS) AF: 0.267 AC: 1289 AN: 4828

European-Finnish (FIN) AF: 0.469 AC: 4954 AN: 10558

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23049 AN: 67984

Other (OTH) AF: 0.274 AC: 578 AN: 2106

Alfa AF: 0.317 Hom.: 5252

Bravo AF: 0.281

Asia WGS AF: 0.297 AC: 1030 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		0.46
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: rs7699742; hg19: chr4-123264485; COSMIC: COSV52691055;