6-34856859-A-G

Variant names:

• chr6-34856859-A-G
• rs11755393
• NM_017754.4:c.1361A>G

Variant summary

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

The NM_017754.4(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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (17562 hom., cov: 33)
  • Exomes 𝑓: 0.35 (93570 hom.)
• Consequence: BLTP3A NM_017754.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 90 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017754.4. 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
	BLTP3A	NM_017754.4	MANE Select	c.1361A>G	p.Gln454Arg	missense	Exon 11 of 21	NP_060224.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP3A	ENST00000192788.6	TSL:1 MANE Select	c.1361A>G	p.Gln454Arg	missense	Exon 11 of 21	ENSP00000192788.5

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

GnomAD2 exomes AF: 0.364 AC: 90668 AN: 248862 AF XY: 0.362

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 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

African (AFR) AF: 0.709 AC: 23724 AN: 33462

American (AMR) AF: 0.269 AC: 12035 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 11366 AN: 26118

East Asian (EAS) AF: 0.382 AC: 15159 AN: 39664

South Asian (SAS) AF: 0.322 AC: 27785 AN: 86160

European-Finnish (FIN) AF: 0.346 AC: 18497 AN: 53390

Middle Eastern (MID) AF: 0.419 AC: 2415 AN: 5766

European-Non Finnish (NFE) AF: 0.340 AC: 378369 AN: 1111662

Other (OTH) AF: 0.378 AC: 22830 AN: 60360

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

African (AFR) AF: 0.702 AC: 29139 AN: 41494

American (AMR) AF: 0.366 AC: 5590 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1474 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2396 AN: 5156

South Asian (SAS) AF: 0.319 AC: 1540 AN: 4832

European-Finnish (FIN) AF: 0.359 AC: 3800 AN: 10590

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23567 AN: 67988

Other (OTH) AF: 0.459 AC: 969 AN: 2112

Alfa AF: 0.391 Hom.: 39834

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 v4.9

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
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.044	T
MetaRNN	Benign	0.0000027	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.71	N
PhyloP100		2.0
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.075
Sift	Benign	0.74	T
Sift4G	Benign	0.69	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
Mutation Taster		=99/1	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: rs11755393; hg19: chr6-34824636; COSMIC: COSV51955557;