Variant 6-26370605-T-G details in Genebe, Genetics Data Aggregator

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

Splicing: ADA: 1.000

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]

BTN3A2 links:

(HGNC:):

links:

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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	UniProt
BTN3A2	NM_007047.5 linkuse as main transcript	c.715+2T>G		splice_donor_variant		ENST00000377708.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
BTN3A2	ENST00000377708.7 linkuse as main transcript	c.715+2T>G	splice_donor_variant	1	NM_007047.5	P2	P78410-1
	ENST00000707189.1 linkuse as main transcript	n.1000-182582T>G	intron_variant, non_coding_transcript_variant
	ENST00000707191.1 linkuse as main transcript	n.1001-162100T>G	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0455

AC:

6922

AN:

152110

Hom.:

166

Cov.:

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.:

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.:

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.:

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 submitter

clinical testing

GeneDx

Apr 27, 2020

This 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

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.94

Eigen

Uncertain

0.50

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.69

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.

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