Genetic Variant BTNL3:p.Phe11Leu (chr5-180989061-C-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_197975.3(BTNL3):c.33C>G(p.Phe11Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00386 in 1,448,098 control chromosomes in the GnomAD database, including 804 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 375 hom., cov: 24)

Exomes 𝑓: 0.0021 ( 429 hom. )

Consequence

BTNL3
NM_197975.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.381

Variant links:

Genes affected

BTNL3 (HGNC:1143): (butyrophilin like 3) Predicted to enable signaling receptor binding activity. Predicted to be involved in T cell receptor signaling pathway and regulation of cytokine production. Predicted to be integral component of membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

BTNL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025765002).

BP6

Variant 5-180989061-C-G is Benign according to our data. Variant chr5-180989061-C-G is described in ClinVar as [Benign]. Clinvar id is 781740.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL3	NM_197975.3 link	c.33C>G	p.Phe11Leu	missense_variant	Exon 1 of 8	ENST00000342868.7	NP_932079.1	Q6UXE8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTNL3	ENST00000342868.7 link	c.33C>G	p.Phe11Leu	missense_variant	Exon 1 of 8	1	NM_197975.3	ENSP00000341787.6		Q6UXE8-1

Frequencies

GnomAD3 genomes

AF:

0.0202

AC:

2774

AN:

137558

Hom.:

375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0654

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00794

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000215

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0132

Gnomad NFE

AF:

0.000399

Gnomad OTH

AF:

0.0190

GnomAD3 exomes

AF:

0.00505

AC:

1048

AN:

207630

Hom.:

119

AF XY:

0.00356

AC XY:

401

AN XY:

112768

show subpopulations

Gnomad AFR exome

AF:

0.0634

Gnomad AMR exome

AF:

0.00355

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000143

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000331

Gnomad OTH exome

AF:

0.00242

GnomAD4 exome

AF:

0.00214

AC:

2804

AN:

1310436

Hom.:

429

Cov.:

AF XY:

0.00178

AC XY:

1164

AN XY:

652374

show subpopulations

Gnomad4 AFR exome

AF:

0.0669

Gnomad4 AMR exome

AF:

0.00417

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000967

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000208

Gnomad4 OTH exome

AF:

0.00465

GnomAD4 genome

AF:

0.0202

AC:

2780

AN:

137662

Hom.:

375

Cov.:

AF XY:

0.0188

AC XY:

1263

AN XY:

67078

show subpopulations

Gnomad4 AFR

AF:

0.0654

Gnomad4 AMR

AF:

0.00793

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000216

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000399

Gnomad4 OTH

AF:

0.0188

Alfa

AF:

0.0168

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0644

AC:

245

ESP6500EA

AF:

0.000264

AC:

ExAC

AF:

0.00596

AC:

665

Asia WGS

AF:

0.00241

AC:

AN:

3328

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 22, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.19

DANN

Benign

0.25

DEOGEN2

Benign

0.0019

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

PrimateAI

Benign

0.39

PROVEAN

Benign

1.4

REVEL

Benign

0.028

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.035

MutPred

0.40

Loss of helix (P = 0.1299);

MVP

0.24

MPC

0.46

ClinPred

0.0022

GERP RS

-0.27

Varity_R

0.039

gMVP

0.049

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over