NM_001384125.1:c.4671+111A>G

Variant names:

• chr4-122240464-A-G
• rs7657746
• NM_001384125.1:c.4671+111A>G

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.4671+111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 859,802 control chromosomes in the GnomAD database, including 23,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4778 hom., cov: 32)
  • Exomes 𝑓: 0.22 (19213 hom.)
• Consequence: BLTP1 NM_001384125.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0280
• Publications: 45 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=-0.88).
• BP6: Variant 4-122240464-A-G is Benign according to our data. Variant chr4-122240464-A-G is described in ClinVar as Benign. ClinVar VariationId is 1244401.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 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.4671+111A>G		intron	N/A	NP_001371054.1
	BLTP1	NM_015312.4		c.4671+111A>G		intron	N/A	NP_056127.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP1	ENST00000679879.1	MANE Select	c.4671+111A>G		intron	N/A	ENSP00000505357.1
	BLTP1	ENST00000388738.8	TSL:1	c.4671+111A>G		intron	N/A	ENSP00000373390.4
	BLTP1	ENST00000446180.5	TSL:1	c.387+111A>G		intron	N/A	ENSP00000394909.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36504 AN: 152028 Hom.: 4781 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.0457

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.220 AC: 155918 AN: 707656 Hom.: 19213 AF XY: 0.217 AC XY: 79273 AN XY: 364758

African (AFR) AF: 0.313 AC: 5328 AN: 17014

American (AMR) AF: 0.150 AC: 3189 AN: 21222

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 3701 AN: 15618

East Asian (EAS) AF: 0.0354 AC: 1168 AN: 33010

South Asian (SAS) AF: 0.133 AC: 6926 AN: 51906

European-Finnish (FIN) AF: 0.136 AC: 4405 AN: 32288

Middle Eastern (MID) AF: 0.223 AC: 894 AN: 4004

European-Non Finnish (NFE) AF: 0.246 AC: 122509 AN: 497930

Other (OTH) AF: 0.225 AC: 7798 AN: 34664

GnomAD4 genome AF: 0.240 AC: 36514 AN: 152146 Hom.: 4778 Cov.: 32 AF XY: 0.230 AC XY: 17094 AN XY: 74386

African (AFR) AF: 0.312 AC: 12940 AN: 41482

American (AMR) AF: 0.182 AC: 2788 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 867 AN: 3468

East Asian (EAS) AF: 0.0452 AC: 234 AN: 5178

South Asian (SAS) AF: 0.124 AC: 600 AN: 4826

European-Finnish (FIN) AF: 0.129 AC: 1370 AN: 10598

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16823 AN: 67994

Other (OTH) AF: 0.247 AC: 522 AN: 2110

Alfa AF: 0.242 Hom.: 7288

Bravo AF: 0.249

Asia WGS AF: 0.116 AC: 404 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.67
PhyloP100		-0.028
PromoterAI		-0.012	Neutral
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: rs7657746; hg19: chr4-123161619;