4-122194347-A-G

Variant names:

• chr4-122194347-A-G
• rs13151961
• NM_001384125.1:c.1052+1968A>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.1052+1968A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 161,474 control chromosomes in the GnomAD database, including 1,260 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 0.11 (1110 hom., cov: 32)
  • Exomes 𝑓: 0.17 (150 hom.)
• Consequence: BLTP1 NM_001384125.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 57 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP1	NM_001384125.1	MANE Select	c.1052+1968A>G		intron	N/A	NP_001371054.1	A0A7P0T938
	BLTP1	NM_015312.4		c.1052+1968A>G		intron	N/A	NP_056127.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP1	ENST00000679879.1	MANE Select	c.1052+1968A>G		intron	N/A	ENSP00000505357.1	A0A7P0T938
	BLTP1	ENST00000388738.8	TSL:1	c.1052+1968A>G		intron	N/A	ENSP00000373390.4	A0A8J8Z0T9
	BLTP1	ENST00000264501.8	TSL:5	c.1052+1968A>G		intron	N/A	ENSP00000264501.4	Q2LD37-1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16208 AN: 152154 Hom.: 1110 Cov.: 32

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.0773

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.0974

GnomAD4 exome AF: 0.167 AC: 1536 AN: 9202 Hom.: 150 AF XY: 0.167 AC XY: 750 AN XY: 4502

African (AFR) AF: 0.0313 AC: 6 AN: 192

American (AMR) AF: 0.00 AC: 0 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 6 AN: 38

East Asian (EAS) AF: 0.00 AC: 0 AN: 32

South Asian (SAS) AF: 0.116 AC: 20 AN: 172

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AF: 0.182 AC: 4 AN: 22

European-Non Finnish (NFE) AF: 0.173 AC: 1452 AN: 8406

Other (OTH) AF: 0.143 AC: 47 AN: 328

GnomAD4 genome AF: 0.106 AC: 16210 AN: 152272 Hom.: 1110 Cov.: 32 AF XY: 0.103 AC XY: 7654 AN XY: 74464

African (AFR) AF: 0.0404 AC: 1680 AN: 41568

American (AMR) AF: 0.0772 AC: 1181 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 340 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.105 AC: 507 AN: 4826

European-Finnish (FIN) AF: 0.107 AC: 1134 AN: 10596

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10971 AN: 68002

Other (OTH) AF: 0.0959 AC: 203 AN: 2116

Alfa AF: 0.144 Hom.: 6322

Bravo AF: 0.0989

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.43
PhyloP100		0.011
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: rs13151961; hg19: chr4-123115502;