chr4-122359705-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong 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

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 4-122359705-T-C is Benign according to our data. Variant chr4-122359705-T-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLTP1	NM_001384125.1	c.15048T>C	p.His5016His	synonymous_variant	Exon 87 of 88	ENST00000679879.1	NP_001371054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLTP1	ENST00000679879.1	c.15048T>C	p.His5016His	synonymous_variant	Exon 87 of 88		NM_001384125.1	ENSP00000505357.1

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

GnomAD3 exomes AF: 0.192 AC: 47580 AN: 247316 Hom.: 5518 AF XY: 0.195 AC XY: 26213 AN XY: 134282

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 SAS exome AF: 0.143

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

Gnomad4 AFR exome AF: 0.0320

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.358

Gnomad4 NFE exome AF: 0.223

Gnomad4 OTH exome AF: 0.187

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

Gnomad4 AFR AF: 0.0387

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.160

Alfa AF: 0.212 Hom.: 8003

Bravo AF: 0.144

Asia WGS AF: 0.110 AC: 382 AN: 3476

EpiCase AF: 0.214

EpiControl AF: 0.214

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.7
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs1127348; hg19: chr4-123280860; COSMIC: COSV52662755;