rs1127348

Variant names:

• chr4-122359705-T-C
• rs1127348
• NM_001384125.1:c.15048T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001384125.1(BLTP1):​c.15048T>C​(p.His5016His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,609,210 control chromosomes in the GnomAD database, including 37,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2832 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34710 hom.)
• Consequence: BLTP1 NM_001384125.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.39
• Publications: 30 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.143).
• BP6: Variant 4-122359705-T-C is Benign according to our data. Variant chr4-122359705-T-C is described in ClinVar as Benign. ClinVar VariationId is 1179225.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 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.15048T>C	p.His5016His	synonymous	Exon 87 of 88	NP_001371054.1
	BLTP1	NM_015312.4		c.14784T>C	p.His4928His	synonymous	Exon 83 of 84	NP_056127.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP1	ENST00000679879.1	MANE Select	c.15048T>C	p.His5016His	synonymous	Exon 87 of 88	ENSP00000505357.1
	BLTP1	ENST00000388738.8	TSL:1	c.14439T>C	p.His4813His	synonymous	Exon 84 of 85	ENSP00000373390.4
	BLTP1	ENST00000306802.8	TSL:1	c.3909T>C	p.His1303His	synonymous	Exon 23 of 24	ENSP00000304374.4

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25275 AN: 151962 Hom.: 2834 Cov.: 32

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.160

GnomAD2 exomes AF: 0.192 AC: 47580 AN: 247316 AF XY: 0.195

Gnomad AFR exome AF: 0.0329

Gnomad AMR exome AF: 0.0991

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.136

Gnomad FIN exome AF: 0.365

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.210 AC: 305689 AN: 1457130 Hom.: 34710 Cov.: 30 AF XY: 0.209 AC XY: 151262 AN XY: 725094

African (AFR) AF: 0.0320 AC: 1067 AN: 33310

American (AMR) AF: 0.103 AC: 4585 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 4865 AN: 26056

East Asian (EAS) AF: 0.123 AC: 4875 AN: 39510

South Asian (SAS) AF: 0.141 AC: 12123 AN: 85952

European-Finnish (FIN) AF: 0.358 AC: 18927 AN: 52806

Middle Eastern (MID) AF: 0.112 AC: 642 AN: 5738

European-Non Finnish (NFE) AF: 0.223 AC: 247340 AN: 1109132

Other (OTH) AF: 0.187 AC: 11265 AN: 60214

GnomAD4 genome AF: 0.166 AC: 25260 AN: 152080 Hom.: 2832 Cov.: 32 AF XY: 0.171 AC XY: 12706 AN XY: 74342

African (AFR) AF: 0.0387 AC: 1608 AN: 41536

American (AMR) AF: 0.131 AC: 1993 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3468

East Asian (EAS) AF: 0.134 AC: 691 AN: 5166

South Asian (SAS) AF: 0.131 AC: 631 AN: 4824

European-Finnish (FIN) AF: 0.365 AC: 3856 AN: 10574

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15315 AN: 67930

Other (OTH) AF: 0.160 AC: 336 AN: 2104

Alfa AF: 0.202 Hom.: 11158

Bravo AF: 0.144

Asia WGS AF: 0.110 AC: 382 AN: 3476

EpiCase AF: 0.214

EpiControl AF: 0.214

ClinVar

ClinVar submissions as Germline

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	-0.48
CADD	Benign	4.7
DANN	Benign	0.66
PhyloP100		2.4
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: rs1127348; hg19: chr4-123280860; COSMIC: COSV52662755;