6-26459733-T-C
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_007049.5(BTN2A1):āc.335T>Cā(p.Ile112Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000052 in 1,614,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000092 ( 0 hom., cov: 32)
Exomes š: 0.000048 ( 0 hom. )
Consequence
BTN2A1
NM_007049.5 missense
NM_007049.5 missense
Scores
4
5
8
Clinical Significance
Conservation
PhyloP100: 4.55
Genes affected
BTN2A1 (HGNC:1136): (butyrophilin subfamily 2 member A1) This gene encodes a member of the immunoglobulin superfamily. The gene is located in a cluster of butyrophilin-like genes in the juxta-telomeric region of the major histocompatibility complex on chromosome 6. A pseudogene of this gene has been identified in this cluster. The encoded protein is an integral plasma membrane protein involved in lipid, fatty-acid, and sterol metabolism. Alterations in this gene may be associated with several disease states including metabolic syndrome. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.036535263).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BTN2A1 | NM_007049.5 | c.335T>C | p.Ile112Thr | missense_variant | 3/8 | ENST00000312541.10 | |
BTN2A1 | NM_001197233.3 | c.152T>C | p.Ile51Thr | missense_variant | 2/7 | ||
BTN2A1 | NM_078476.4 | c.335T>C | p.Ile112Thr | missense_variant | 3/8 | ||
BTN2A1 | NM_001197234.3 | c.335T>C | p.Ile112Thr | missense_variant | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BTN2A1 | ENST00000312541.10 | c.335T>C | p.Ile112Thr | missense_variant | 3/8 | 1 | NM_007049.5 | P1 | |
ENST00000707189.1 | n.1000-93454T>C | intron_variant, non_coding_transcript_variant | |||||||
ENST00000707191.1 | n.1001-72972T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152116Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000183 AC: 46AN: 251462Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135910
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GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 32AN XY: 727246
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GnomAD4 genome AF: 0.0000920 AC: 14AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74452
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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 | Feb 11, 2022 | The c.335T>C (p.I112T) alteration is located in exon 3 (coding exon 2) of the BTN2A1 gene. This alteration results from a T to C substitution at nucleotide position 335, causing the isoleucine (I) at amino acid position 112 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;T;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Benign
Sift
Pathogenic
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
1.0
.;D;.;.;.
Vest4
MVP
MPC
0.42
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at