Genetic Variant BTNL8:p.Ser179Phe (chr5-180911477-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001040462.3(BTNL8):c.536C>T(p.Ser179Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000269 in 1,614,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

BTNL8
NM_001040462.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.734

Publications

2 publications found

Variant links:

Genes affected

BTNL8 (HGNC:26131): (butyrophilin like 8) 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 located in plasma membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

BTNL8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025084168).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040462.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTNL8	NM_001040462.3	MANE Select	c.536C>T	p.Ser179Phe	missense	Exon 3 of 8	NP_001035552.1	Q6UX41-1
BTNL8	NM_001159707.2		c.188C>T	p.Ser63Phe	missense	Exon 2 of 7	NP_001153179.1	Q6UX41-6
BTNL8	NM_001159709.2		c.161C>T	p.Ser54Phe	missense	Exon 3 of 8	NP_001153181.1	Q6UX41-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTNL8	ENST00000340184.9	TSL:1 MANE Select	c.536C>T	p.Ser179Phe	missense	Exon 3 of 8	ENSP00000342197.4	Q6UX41-1
BTNL8	ENST00000511704.5	TSL:1	c.188C>T	p.Ser63Phe	missense	Exon 2 of 7	ENSP00000425207.1	Q6UX41-6
BTNL8	ENST00000231229.8	TSL:1	c.536C>T	p.Ser179Phe	missense	Exon 3 of 8	ENSP00000231229.4	Q6UX41-5

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000119

AC:

AN:

251468

AF XY:

0.000118

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000283

AC:

413

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

196

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000361

AC:

401

AN:

1112010

Other (OTH)

AF:

0.000149

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

122

153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000138

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41562

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000189

Hom.:

Bravo

AF:

0.000132

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.0

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.016

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.67

M_CAP

Benign

0.0028

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

-0.73

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.7

REVEL

Benign

0.028

Sift

Benign

0.039

Sift4G

Benign

0.24

Polyphen

0.026

Vest4

0.17

MVP

0.19

MPC

0.16

ClinPred

0.046

GERP RS

1.7

Varity_R

0.036

gMVP

0.052

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over