4-122174734-G-C

Variant names:

• chr4-122174734-G-C
• rs73844482
• NM_001384125.1:c.293+82G>C

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.293+82G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,068,098 control chromosomes in the GnomAD database, including 259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (135 hom., cov: 32)
  • Exomes 𝑓: 0.0099 (124 hom.)
• Consequence: BLTP1 NM_001384125.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.222
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-122174734-G-C is Benign according to our data. Variant chr4-122174734-G-C is described in ClinVar as Benign. ClinVar VariationId is 1229274.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0778 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.293+82G>C		intron	N/A	NP_001371054.1	A0A7P0T938
	BLTP1	NM_015312.4		c.293+82G>C		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.293+82G>C		intron	N/A	ENSP00000505357.1	A0A7P0T938
	BLTP1	ENST00000388738.8	TSL:1	c.293+82G>C		intron	N/A	ENSP00000373390.4	A0A8J8Z0T9
	BLTP1	ENST00000264501.8	TSL:5	c.293+82G>C		intron	N/A	ENSP00000264501.4	Q2LD37-1

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4299 AN: 152040 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00703

Gnomad OTH AF: 0.0283

GnomAD4 exome AF: 0.00990 AC: 9066 AN: 915940 Hom.: 124 AF XY: 0.0104 AC XY: 4830 AN XY: 466530

African (AFR) AF: 0.0803 AC: 1547 AN: 19270

American (AMR) AF: 0.0107 AC: 244 AN: 22756

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 295 AN: 18892

East Asian (EAS) AF: 0.000591 AC: 19 AN: 32132

South Asian (SAS) AF: 0.0295 AC: 1632 AN: 55344

European-Finnish (FIN) AF: 0.00108 AC: 49 AN: 45378

Middle Eastern (MID) AF: 0.0171 AC: 52 AN: 3034

European-Non Finnish (NFE) AF: 0.00692 AC: 4696 AN: 678826

Other (OTH) AF: 0.0132 AC: 532 AN: 40308

GnomAD4 genome AF: 0.0283 AC: 4304 AN: 152158 Hom.: 135 Cov.: 32 AF XY: 0.0278 AC XY: 2067 AN XY: 74390

African (AFR) AF: 0.0801 AC: 3324 AN: 41516

American (AMR) AF: 0.0145 AC: 221 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0307 AC: 148 AN: 4826

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10586

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00703 AC: 478 AN: 67982

Other (OTH) AF: 0.0280 AC: 59 AN: 2106

Alfa AF: 0.0162 Hom.: 3

Bravo AF: 0.0313

Asia WGS AF: 0.0190 AC: 66 AN: 3464

ClinVar

ClinVar submissions

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	-0.81
CADD	Benign	4.6
DANN	Benign	0.76
PhyloP100		-0.22
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: rs73844482; hg19: chr4-123095889;