4-122266714-C-T

Variant names:

• chr4-122266714-C-T
• rs7683061
• NM_001384125.1:c.7318-69C>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.7318-69C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,359,304 control chromosomes in the GnomAD database, including 105,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11129 hom., cov: 31)
  • Exomes 𝑓: 0.39 (94207 hom.)
• Consequence: BLTP1 NM_001384125.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.558
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-122266714-C-T is Benign according to our data. Variant chr4-122266714-C-T is described in ClinVar as Benign. ClinVar VariationId is 1225841.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLTP1	NM_001384125.1	c.7318-69C>T		intron_variant	Intron 45 of 87	ENST00000679879.1	NP_001371054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLTP1	ENST00000679879.1	c.7318-69C>T		intron_variant	Intron 45 of 87		NM_001384125.1	ENSP00000505357.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58000 AN: 151742 Hom.: 11112 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.391 AC: 472275 AN: 1207444 Hom.: 94207 Cov.: 16 AF XY: 0.396 AC XY: 235996 AN XY: 595908

African (AFR) AF: 0.362 AC: 9004 AN: 24848

American (AMR) AF: 0.359 AC: 8241 AN: 22976

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 8766 AN: 17836

East Asian (EAS) AF: 0.357 AC: 12004 AN: 33608

South Asian (SAS) AF: 0.542 AC: 31071 AN: 57302

European-Finnish (FIN) AF: 0.384 AC: 17779 AN: 46292

Middle Eastern (MID) AF: 0.563 AC: 2765 AN: 4914

European-Non Finnish (NFE) AF: 0.381 AC: 362118 AN: 949846

Other (OTH) AF: 0.412 AC: 20527 AN: 49822

GnomAD4 genome AF: 0.382 AC: 58061 AN: 151860 Hom.: 11129 Cov.: 31 AF XY: 0.387 AC XY: 28711 AN XY: 74194

African (AFR) AF: 0.355 AC: 14700 AN: 41384

American (AMR) AF: 0.371 AC: 5663 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1678 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1892 AN: 5164

South Asian (SAS) AF: 0.542 AC: 2609 AN: 4816

European-Finnish (FIN) AF: 0.392 AC: 4132 AN: 10532

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26000 AN: 67924

Other (OTH) AF: 0.411 AC: 866 AN: 2106

Alfa AF: 0.394 Hom.: 9252

Bravo AF: 0.376

Asia WGS AF: 0.452 AC: 1574 AN: 3478

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.46
PhyloP100		-0.56
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: rs7683061; hg19: chr4-123187869; COSMIC: COSV52670509;