chr6-26383878-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_006995.5(BTN2A2):​c.57G>A​(p.Leu19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,613,780 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.010 ( 13 hom., cov: 31)
Exomes 𝑓: 0.012 ( 146 hom. )

Consequence

BTN2A2
NM_006995.5 synonymous

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.145
Variant links:
Genes affected
BTN2A2 (HGNC:1137): (butyrophilin subfamily 2 member A2) Butyrophilin is the major protein associated with fat droplets in the milk. This gene is a member of the BTN2 subfamily of genes, which encode proteins belonging to the butyrophilin protein family. The gene is located in a cluster on chromosome 6, consisting of seven genes belonging to the expanding B7/butyrophilin-like group, a subset of the immunoglobulin gene superfamily. The encoded protein is a type I receptor glycoprotein involved in lipid, fatty-acid and sterol metabolism. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 6-26383878-G-A is Benign according to our data. Variant chr6-26383878-G-A is described in ClinVar as [Benign]. Clinvar id is 3057121.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-0.145 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0101 (1531/152120) while in subpopulation AMR AF= 0.0193 (294/15272). AF 95% confidence interval is 0.0174. There are 13 homozygotes in gnomad4. There are 734 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BTN2A2NM_006995.5 linkuse as main transcriptc.57G>A p.Leu19= synonymous_variant 2/8 ENST00000356709.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BTN2A2ENST00000356709.9 linkuse as main transcriptc.57G>A p.Leu19= synonymous_variant 2/81 NM_006995.5 P1Q8WVV5-1
ENST00000707189.1 linkuse as main transcriptn.1000-169309G>A intron_variant, non_coding_transcript_variant
ENST00000707191.1 linkuse as main transcriptn.1001-148827G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.0101
AC:
1533
AN:
152002
Hom.:
14
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00237
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0193
Gnomad ASJ
AF:
0.0363
Gnomad EAS
AF:
0.00232
Gnomad SAS
AF:
0.0106
Gnomad FIN
AF:
0.00226
Gnomad MID
AF:
0.0285
Gnomad NFE
AF:
0.0131
Gnomad OTH
AF:
0.0125
GnomAD3 exomes
AF:
0.0114
AC:
2848
AN:
249958
Hom.:
29
AF XY:
0.0122
AC XY:
1649
AN XY:
135064
show subpopulations
Gnomad AFR exome
AF:
0.00179
Gnomad AMR exome
AF:
0.0113
Gnomad ASJ exome
AF:
0.0446
Gnomad EAS exome
AF:
0.00109
Gnomad SAS exome
AF:
0.0125
Gnomad FIN exome
AF:
0.00251
Gnomad NFE exome
AF:
0.0126
Gnomad OTH exome
AF:
0.0178
GnomAD4 exome
AF:
0.0123
AC:
18026
AN:
1461660
Hom.:
146
Cov.:
31
AF XY:
0.0126
AC XY:
9177
AN XY:
727154
show subpopulations
Gnomad4 AFR exome
AF:
0.00197
Gnomad4 AMR exome
AF:
0.0130
Gnomad4 ASJ exome
AF:
0.0411
Gnomad4 EAS exome
AF:
0.000428
Gnomad4 SAS exome
AF:
0.0139
Gnomad4 FIN exome
AF:
0.00221
Gnomad4 NFE exome
AF:
0.0126
Gnomad4 OTH exome
AF:
0.0141
GnomAD4 genome
AF:
0.0101
AC:
1531
AN:
152120
Hom.:
13
Cov.:
31
AF XY:
0.00987
AC XY:
734
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.00239
Gnomad4 AMR
AF:
0.0193
Gnomad4 ASJ
AF:
0.0363
Gnomad4 EAS
AF:
0.00232
Gnomad4 SAS
AF:
0.0104
Gnomad4 FIN
AF:
0.00226
Gnomad4 NFE
AF:
0.0131
Gnomad4 OTH
AF:
0.0123
Alfa
AF:
0.0111
Hom.:
3
Bravo
AF:
0.0115
Asia WGS
AF:
0.00664
AC:
23
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

BTN2A2-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesApr 29, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
1.5
DANN
Benign
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs115247877; hg19: chr6-26384106; API