6-26506707-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001732.3(BTN1A1):​c.734C>T​(p.Pro245Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BTN1A1
NM_001732.3 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06
Variant links:
Genes affected
BTN1A1 (HGNC:1135): (butyrophilin subfamily 1 member A1) Butyrophilin is the major protein associated with fat droplets in the milk. It is a member of the immunoglobulin superfamily. It may have a cell surface receptor function. The human butyrophilin gene is localized in the major histocompatibility complex (MHC) class I region of 6p and may have arisen relatively recently in evolution by the shuffling of exons between 2 ancestral gene families [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BTN1A1NM_001732.3 linkc.734C>T p.Pro245Leu missense_variant Exon 5 of 8 ENST00000684113.1 NP_001723.2 Q13410Q4VAN2
LOC107986583XR_001744057.3 linkn.5890+14802G>A intron_variant Intron 1 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BTN1A1ENST00000684113.1 linkc.734C>T p.Pro245Leu missense_variant Exon 5 of 8 NM_001732.3 ENSP00000507193.1 Q13410
BTN1A1ENST00000244513.10 linkc.734C>T p.Pro245Leu missense_variant Exon 4 of 7 1 ENSP00000244513.6 Q13410
ENSG00000291336ENST00000707189.1 linkn.1000-46480C>T intron_variant Intron 1 of 1
ENSG00000291338ENST00000707191.1 linkn.1001-25998C>T intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251412
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461810
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.734C>T (p.P245L) alteration is located in exon 4 (coding exon 4) of the BTN1A1 gene. This alteration results from a C to T substitution at nucleotide position 734, causing the proline (P) at amino acid position 245 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.089
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
22
DANN
Benign
0.92
DEOGEN2
Uncertain
0.50
T;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.74
T;T
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.47
T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Uncertain
2.8
M;.
PrimateAI
Benign
0.35
T
PROVEAN
Pathogenic
-6.8
D;.
REVEL
Benign
0.20
Sift
Benign
0.076
T;.
Sift4G
Uncertain
0.044
D;D
Polyphen
0.99
D;.
Vest4
0.23
MutPred
0.44
Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP
0.70
MPC
0.48
ClinPred
0.75
D
GERP RS
4.8
Varity_R
0.23
gMVP
0.33

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: rs772232443; hg19: chr6-26506935; API