NM_001384125.1:c.2247+928C>G

Variant names:

• chr4-122212023-C-G
• rs6827444
• NM_001384125.1:c.2247+928C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384125.1(BLTP1):​c.2247+928C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 976,296 control chromosomes in the GnomAD database, including 17,732 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2184 hom., cov: 32)
  • Exomes 𝑓: 0.19 (15548 hom.)
• Consequence: BLTP1 NM_001384125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLTP1	NM_001384125.1	c.2247+928C>G		intron_variant	Intron 20 of 87	ENST00000679879.1	NP_001371054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLTP1	ENST00000679879.1	c.2247+928C>G		intron_variant	Intron 20 of 87		NM_001384125.1	ENSP00000505357.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22812 AN: 151828 Hom.: 2178 Cov.: 32

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.175

GnomAD4 exome AF: 0.191 AC: 157427 AN: 824350 Hom.: 15548 Cov.: 18 AF XY: 0.191 AC XY: 72832 AN XY: 380940

African (AFR) AF: 0.0250 AC: 393 AN: 15718

American (AMR) AF: 0.256 AC: 250 AN: 976

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 1080 AN: 5076

East Asian (EAS) AF: 0.219 AC: 786 AN: 3588

South Asian (SAS) AF: 0.214 AC: 3478 AN: 16270

European-Finnish (FIN) AF: 0.146 AC: 40 AN: 274

Middle Eastern (MID) AF: 0.233 AC: 373 AN: 1598

European-Non Finnish (NFE) AF: 0.193 AC: 145480 AN: 753876

Other (OTH) AF: 0.206 AC: 5547 AN: 26974

GnomAD4 genome AF: 0.150 AC: 22834 AN: 151946 Hom.: 2184 Cov.: 32 AF XY: 0.150 AC XY: 11144 AN XY: 74274

African (AFR) AF: 0.0390 AC: 1616 AN: 41476

American (AMR) AF: 0.213 AC: 3250 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 744 AN: 3466

East Asian (EAS) AF: 0.215 AC: 1110 AN: 5160

South Asian (SAS) AF: 0.212 AC: 1019 AN: 4804

European-Finnish (FIN) AF: 0.135 AC: 1425 AN: 10558

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.191 AC: 12982 AN: 67920

Other (OTH) AF: 0.181 AC: 381 AN: 2108

Alfa AF: 0.0849 Hom.: 139

Bravo AF: 0.152

Asia WGS AF: 0.219 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.23
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6827444; hg19: chr4-123133178;