Genetic Variant BTNL3:p.Arg130Trp (chr5-180993151-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_197975.3(BTNL3):c.388C>T(p.Arg130Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,436,386 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00060 ( 19 hom., cov: 24)

Exomes 𝑓: 0.00079 ( 162 hom. )

Consequence

BTNL3
NM_197975.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.73

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011764735).

BP6

Variant 5-180993151-C-T is Benign according to our data. Variant chr5-180993151-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 738102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTNL3	NM_197975.3 link	c.388C>T	p.Arg130Trp	missense_variant	Exon 2 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.388C>T	p.Arg130Trp	missense_variant	Exon 2 of 8	1	NM_197975.3	ENSP00000341787.6		Q6UXE8-1

Frequencies

GnomAD3 genomes

AF:

0.000601

AC:

AN:

136438

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000504

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00155

Gnomad ASJ

AF:

0.000602

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00742

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00331

Gnomad NFE

AF:

0.000352

Gnomad OTH

AF:

0.00106

GnomAD3 exomes

AF:

0.00140

AC:

256

AN:

183420

Hom.:

AF XY:

0.00159

AC XY:

157

AN XY:

98932

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000382

Gnomad ASJ exome

AF:

0.00114

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00743

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.00301

GnomAD4 exome

AF:

0.000792

AC:

1029

AN:

1299842

Hom.:

162

Cov.:

AF XY:

0.00100

AC XY:

647

AN XY:

645414

show subpopulations

Gnomad4 AFR exome

AF:

0.000154

Gnomad4 AMR exome

AF:

0.000360

Gnomad4 ASJ exome

AF:

0.00159

Gnomad4 EAS exome

AF:

0.0000570

Gnomad4 SAS exome

AF:

0.00693

Gnomad4 FIN exome

AF:

0.0000220

Gnomad4 NFE exome

AF:

0.000266

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.000601

AC:

AN:

136544

Hom.:

Cov.:

AF XY:

0.000633

AC XY:

AN XY:

66390

show subpopulations

Gnomad4 AFR

AF:

0.0000503

Gnomad4 AMR

AF:

0.00155

Gnomad4 ASJ

AF:

0.000602

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00744

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000352

Gnomad4 OTH

AF:

0.00105

Alfa

AF:

0.000572

Hom.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00127

AC:

140

Asia WGS

AF:

0.00543

AC:

AN:

3326

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BTNL3: BP4, BS2 -

Aug 15, 2018

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

0.15

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.085

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.53

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.11

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.013

Polyphen

0.96

Vest4

0.16

MVP

0.21

MPC

0.92

ClinPred

0.15

GERP RS

-5.8

Varity_R

0.12

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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