6-26370605-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 4P and 10B. PVS1_StrongBP6_ModerateBA1

The NM_007047.5(BTN3A2):​c.715+2T>G variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 1,613,974 control chromosomes in the GnomAD database, including 1,347 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.046 ( 166 hom., cov: 32)
Exomes 𝑓: 0.038 ( 1181 hom. )

Consequence

BTN3A2
NM_007047.5 splice_donor

Scores

1
6
Splicing: ADA: 1.000
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.84
Variant links:
Genes affected
BTN3A2 (HGNC:1139): (butyrophilin subfamily 3 member A2) This gene encodes a member of the immunoglobulin superfamily, which resides in the juxta-telomeric region of the major histocompatability class 1 locus and is clustered with the other family members on chromosome 6. The encoded protein may be involved in the adaptive immune response. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.279602 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
BP6
Variant 6-26370605-T-G is Benign according to our data. Variant chr6-26370605-T-G is described in ClinVar as [Benign]. Clinvar id is 1238754.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BTN3A2NM_007047.5 linkuse as main transcriptc.715+2T>G splice_donor_variant ENST00000377708.7 NP_008978.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BTN3A2ENST00000377708.7 linkuse as main transcriptc.715+2T>G splice_donor_variant 1 NM_007047.5 ENSP00000366937 P2P78410-1
ENST00000707189.1 linkuse as main transcriptn.1000-182582T>G intron_variant, non_coding_transcript_variant
ENST00000707191.1 linkuse as main transcriptn.1001-162100T>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0455
AC:
6922
AN:
152110
Hom.:
166
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0676
Gnomad AMI
AF:
0.00877
Gnomad AMR
AF:
0.0390
Gnomad ASJ
AF:
0.0557
Gnomad EAS
AF:
0.00424
Gnomad SAS
AF:
0.0451
Gnomad FIN
AF:
0.0108
Gnomad MID
AF:
0.0633
Gnomad NFE
AF:
0.0419
Gnomad OTH
AF:
0.0483
GnomAD3 exomes
AF:
0.0373
AC:
9351
AN:
250676
Hom.:
229
AF XY:
0.0379
AC XY:
5142
AN XY:
135548
show subpopulations
Gnomad AFR exome
AF:
0.0695
Gnomad AMR exome
AF:
0.0283
Gnomad ASJ exome
AF:
0.0536
Gnomad EAS exome
AF:
0.00348
Gnomad SAS exome
AF:
0.0479
Gnomad FIN exome
AF:
0.0121
Gnomad NFE exome
AF:
0.0411
Gnomad OTH exome
AF:
0.0428
GnomAD4 exome
AF:
0.0377
AC:
55135
AN:
1461746
Hom.:
1181
Cov.:
34
AF XY:
0.0384
AC XY:
27914
AN XY:
727164
show subpopulations
Gnomad4 AFR exome
AF:
0.0699
Gnomad4 AMR exome
AF:
0.0298
Gnomad4 ASJ exome
AF:
0.0585
Gnomad4 EAS exome
AF:
0.00287
Gnomad4 SAS exome
AF:
0.0476
Gnomad4 FIN exome
AF:
0.0123
Gnomad4 NFE exome
AF:
0.0380
Gnomad4 OTH exome
AF:
0.0415
GnomAD4 genome
AF:
0.0455
AC:
6928
AN:
152228
Hom.:
166
Cov.:
32
AF XY:
0.0442
AC XY:
3288
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.0677
Gnomad4 AMR
AF:
0.0389
Gnomad4 ASJ
AF:
0.0557
Gnomad4 EAS
AF:
0.00425
Gnomad4 SAS
AF:
0.0449
Gnomad4 FIN
AF:
0.0108
Gnomad4 NFE
AF:
0.0419
Gnomad4 OTH
AF:
0.0478
Alfa
AF:
0.0433
Hom.:
64
Bravo
AF:
0.0486
ESP6500AA
AF:
0.0676
AC:
298
ESP6500EA
AF:
0.0451
AC:
388
ExAC
AF:
0.0389
AC:
4725
Asia WGS
AF:
0.0330
AC:
116
AN:
3478
EpiCase
AF:
0.0455
EpiControl
AF:
0.0447

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxApr 27, 2020This variant is associated with the following publications: (PMID: 31679996) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
22
DANN
Benign
0.94
Eigen
Uncertain
0.50
Eigen_PC
Benign
0.18
FATHMM_MKL
Benign
0.69
D
MutationTaster
Benign
1.0
D;D;D;D;D;D
GERP RS
2.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.86
SpliceAI score (max)
0.98
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.98
Position offset: -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.

Other links and lift over

dbSNP: rs58367598; hg19: chr6-26370833; COSMIC: COSV62687406; COSMIC: COSV62687406; API