Variant 5-180950044-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001040462.3(BTNL8):c.1003A>G(p.Ser335Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000985 in 1,462,180 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 3 hom., cov: 22)

Exomes 𝑓: 0.000091 ( 18 hom. )

Consequence

BTNL8
NM_001040462.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.168

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019043297).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTNL8	NM_001040462.3 linkuse as main transcript	c.1003A>G	p.Ser335Gly	missense_variant	8/8	ENST00000340184.9	NP_001035552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTNL8	ENST00000340184.9 linkuse as main transcript	c.1003A>G	p.Ser335Gly	missense_variant	8/8	1	NM_001040462.3	ENSP00000342197	P1	Q6UX41-1

Frequencies

GnomAD3 genomes

AF:

0.000170

AC:

AN:

134950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000382

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000237

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000661

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000339

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

230332

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

125354

show subpopulations

Gnomad AFR exome

AF:

0.000327

Gnomad AMR exome

AF:

0.0000638

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000578

Gnomad SAS exome

AF:

0.000399

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000490

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000912

AC:

121

AN:

1327128

Hom.:

Cov.:

AF XY:

0.0000952

AC XY:

AN XY:

661722

show subpopulations

Gnomad4 AFR exome

AF:

0.000486

Gnomad4 AMR exome

AF:

0.000173

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000567

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000430

Gnomad4 OTH exome

AF:

0.000126

GnomAD4 genome

AF:

0.000170

AC:

AN:

135052

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

AN XY:

65586

show subpopulations

Gnomad4 AFR

AF:

0.000381

Gnomad4 AMR

AF:

0.000237

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000662

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000339

Gnomad4 OTH

AF:

0.00

ESP6500AA

AF:

0.000466

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

The c.1003A>G (p.S335G) alteration is located in exon 8 (coding exon 8) of the BTNL8 gene. This alteration results from a A to G substitution at nucleotide position 1003, causing the serine (S) at amino acid position 335 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.053

DANN

Benign

0.65

DEOGEN2

Benign

0.0026

T;.;.;.;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00070

LIST_S2

Benign

0.14

T;.;T;T;T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.019

T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.67

N;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.13

N;N;N;.;N;N

REVEL

Benign

0.010

Sift

Benign

0.60

T;T;T;.;T;T

Sift4G

Benign

0.69

T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;.

Vest4

0.072

MVP

0.11

MPC

0.13

ClinPred

0.0024

GERP RS

-0.38

Varity_R

0.036

gMVP

0.13

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

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