rs11755393

Positions:

• chr6-34856859-A-G
• chr6-34856859-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000192788.6(BLTP3A):​c.1361A>G​(p.Gln454Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,613,382 control chromosomes in the GnomAD database, including 111,132 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.45 (17562 hom., cov: 33)
  • Exomes 𝑓: 0.35 (93570 hom.)
• Consequence: BLTP3A ENST00000192788.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

Genes affected

BLTP3A (HGNC:21216): (bridge-like lipid transfer protein family member 3A) Enables histone deacetylase binding activity and identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.745732E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLTP3A	NM_017754.4	c.1361A>G	p.Gln454Arg	missense_variant	11/21	ENST00000192788.6	NP_060224.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLTP3A	ENST00000192788.6	c.1361A>G	p.Gln454Arg	missense_variant	11/21	1	NM_017754.4	ENSP00000192788	P1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68772 AN: 152014 Hom.: 17510 Cov.: 33

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.457

GnomAD3 exomes AF: 0.364 AC: 90668 AN: 248862 Hom.: 18057 AF XY: 0.362 AC XY: 48840 AN XY: 134990

Gnomad AFR exome AF: 0.701

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.435

Gnomad EAS exome AF: 0.459

Gnomad SAS exome AF: 0.317

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.360

GnomAD4 exome AF: 0.351 AC: 512180 AN: 1461250 Hom.: 93570 Cov.: 40 AF XY: 0.350 AC XY: 254708 AN XY: 726886

Gnomad4 AFR exome AF: 0.709

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.435

Gnomad4 EAS exome AF: 0.382

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.453 AC: 68872 AN: 152132 Hom.: 17562 Cov.: 33 AF XY: 0.452 AC XY: 33573 AN XY: 74356

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.459

Alfa AF: 0.371 Hom.: 22785

Bravo AF: 0.466

TwinsUK AF: 0.347 AC: 1287

ALSPAC AF: 0.335 AC: 1292

ESP6500AA AF: 0.662 AC: 2549

ESP6500EA AF: 0.350 AC: 2892

ExAC AF: 0.368 AC: 44466

Asia WGS AF: 0.373 AC: 1299 AN: 3478

EpiCase AF: 0.356

EpiControl AF: 0.357

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.0053	T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.044	T;T
MetaRNN	Benign	0.0000027	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.71	.;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.040	N;N
REVEL	Benign	0.075
Sift	Benign	0.74	T;T
Sift4G	Benign	0.69	T;T
Polyphen		0.0	.;B
Vest4		0.011
MPC		0.14
ClinPred		0.0041	T
GERP RS		5.0
Varity_R		0.024
gMVP		0.26

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: rs11755393; hg19: chr6-34824636; COSMIC: COSV51955557;