Genetic Variant NM_001304561.2:c.1360G>T (chr6-32394744-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001304561.2(BTNL2):c.1360G>T(p.Glu454*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,610,994 control chromosomes in the GnomAD database, including 1,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.012 ( 67 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1054 hom. )

Consequence

BTNL2
NM_001304561.2 stop_gained, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.81

Publications

21 publications found

Variant links:

Genes affected

BTNL2 (HGNC:1142): (butyrophilin like 2) This gene encodes a major histocompatibility complex, class II associated, type I transmembrane protein which belongs to the butyrophilin-like B7 family of immunoregulators. It is thought to be involved in immune surveillance, serving as a negative T-cell regulator by decreasing T-cell proliferation and cytokine release. The encoded protein contains an N-terminal signal peptide, two pairs of immunoglobulin-like domains, separated by a heptad peptide sequence, and a C-terminal transmembrane domain. Naturally occurring mutations in this gene are associated with sarcoidosis, rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease, myositis, type 1 diabetes, systemic lupus erythematosus, acute coronary syndrome, and prostate cancer. [provided by RefSeq, May 2017]

BTNL2 links:

TSBP1-AS1 (HGNC:39756): (TSBP1 and BTNL2 antisense RNA 1)

TSBP1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304561.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL2	NM_001304561.2	MANE Select	c.1360G>T	p.Glu454*	stop_gained splice_region	Exon 6 of 8	NP_001291490.1	Q9UIR0-7
	TSBP1-AS1	NR_136245.1		n.303-10710C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTNL2	ENST00000454136.8	TSL:5 MANE Select	c.1360G>T	p.Glu454*	stop_gained splice_region	Exon 6 of 8	ENSP00000390613.3	Q9UIR0-7
BTNL2	ENST00000465865.6	TSL:1	n.*631G>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000420063.1	F8WDK6
BTNL2	ENST00000544175.3	TSL:1	n.*621G>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000443364.2	Q9UIR0-8

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1861

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00923

Gnomad ASJ

AF:

0.0452

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00551

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0228

AC:

5712

AN:

250106

AF XY:

0.0259

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00936

Gnomad ASJ exome

AF:

0.0492

Gnomad EAS exome

AF:

0.0821

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00689

Gnomad OTH exome

AF:

0.0216

GnomAD4 exome

AF:

0.0154

AC:

22420

AN:

1458668

Hom.:

1054

Cov.:

AF XY:

0.0178

AC XY:

12895

AN XY:

725040

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

33432

American (AMR)

AF:

0.00990

AC:

442

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.0487

AC:

1269

AN:

26054

East Asian (EAS)

AF:

0.161

AC:

6393

AN:

39598

South Asian (SAS)

AF:

0.0824

AC:

7081

AN:

85920

European-Finnish (FIN)

AF:

0.000262

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.0382

AC:

220

AN:

5756

European-Non Finnish (NFE)

AF:

0.00522

AC:

5787

AN:

1109636

Other (OTH)

AF:

0.0193

AC:

1165

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

991

1982

2973

3964

4955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.0122

AC:

1859

AN:

152326

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1055

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41572

American (AMR)

AF:

0.00921

AC:

141

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0452

AC:

157

AN:

3472

East Asian (EAS)

AF:

0.110

AC:

567

AN:

5178

South Asian (SAS)

AF:

0.100

AC:

483

AN:

4828

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00551

AC:

375

AN:

68036

Other (OTH)

AF:

0.0147

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

169

253

338

422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0103

Hom.:

Bravo

AF:

0.00989

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00814

AC:

ExAC

AF:

0.0235

AC:

2858

Asia WGS

AF:

0.0810

AC:

282

AN:

3478

EpiCase

AF:

0.00780

EpiControl

AF:

0.00694

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

(source)

DANN

Benign

0.97

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.53

FATHMM_MKL

Uncertain

0.83

PhyloP100

1.8

Vest4

0.28

ClinPred

0.068

GERP RS

2.1

Varity_R

0.12

Mutation Taster

=186/14

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.38

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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