chr6-26370570-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_007047.5(BTN3A2):​c.682G>A​(p.Gly228Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,614,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

BTN3A2
NM_007047.5 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.29
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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.031030387).
BP6
Variant 6-26370570-G-A is Benign according to our data. Variant chr6-26370570-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2220871.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BTN3A2NM_007047.5 linkuse as main transcriptc.682G>A p.Gly228Ser missense_variant 5/11 ENST00000377708.7 NP_008978.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BTN3A2ENST00000377708.7 linkuse as main transcriptc.682G>A p.Gly228Ser missense_variant 5/111 NM_007047.5 ENSP00000366937 P2P78410-1
ENST00000707189.1 linkuse as main transcriptn.1000-182617G>A intron_variant, non_coding_transcript_variant
ENST00000707191.1 linkuse as main transcriptn.1001-162135G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000796
AC:
20
AN:
251312
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135844
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000792
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000114
AC:
167
AN:
1461880
Hom.:
0
Cov.:
34
AF XY:
0.000109
AC XY:
79
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000123
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152278
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000135
Hom.:
0
Bravo
AF:
0.0000869
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10

ClinVar

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

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsNov 18, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
0.35
DANN
Benign
0.60
DEOGEN2
Benign
0.037
.;.;.;T;T;T;T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0068
N
LIST_S2
Benign
0.71
T;T;T;.;.;.;T;T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.031
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.91
.;.;.;L;L;L;L;.
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Benign
0.23
T
PROVEAN
Uncertain
-3.2
D;D;D;D;D;D;D;.
REVEL
Benign
0.020
Sift
Benign
0.15
T;T;T;T;T;T;T;.
Sift4G
Benign
0.91
T;T;T;T;T;T;T;T
Polyphen
0.0020
.;.;.;B;B;B;B;.
Vest4
0.054, 0.050, 0.066
MVP
0.15
MPC
0.084
ClinPred
0.013
T
GERP RS
-2.8
Varity_R
0.083
gMVP
0.056

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs373600244; hg19: chr6-26370798; COSMIC: COSV62687782; COSMIC: COSV62687782; API