6-26409662-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007048.6(BTN3A1):c.845G>C(p.Arg282Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 1,599,422 control chromosomes in the GnomAD database, including 6,272 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.047 (255 hom., cov: 31)
  • Exomes 𝑓: 0.081 (6017 hom.)
• Consequence: BTN3A1 NM_007048.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.25

Genes affected

BTN3A1 (HGNC:1138): (butyrophilin subfamily 3 member A1) The butyrophilin (BTN) genes are a group of major histocompatibility complex (MHC)-associated genes that encode type I membrane proteins with 2 extracellular immunoglobulin (Ig) domains and an intracellular B30.2 (PRYSPRY) domain. Three subfamilies of human BTN genes are located in the MHC class I region: the single-copy BTN1A1 gene (MIM 601610) and the BTN2 (e.g., BTN2A1; MIM 613590) and BTN3 (e.g., BNT3A1) genes, which have undergone tandem duplication, resulting in 3 copies of each (summary by Smith et al., 2010 [PubMed 20208008]).[supplied by OMIM, Nov 2010]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023488998).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTN3A1	NM_007048.6	c.845G>C	p.Arg282Thr	missense_variant	5/10	ENST00000289361.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTN3A1	ENST00000289361.11	c.845G>C	p.Arg282Thr	missense_variant	5/10	1	NM_007048.6	P1
	ENST00000707189.1	n.1000-143525G>C		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1001-123043G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0466 AC: 7087 AN: 152080 Hom.: 255 Cov.: 31

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.0330

GnomAD3 exomes AF: 0.0446 AC: 10575 AN: 236930 Hom.: 421 AF XY: 0.0443 AC XY: 5722 AN XY: 129074

Gnomad AFR exome AF: 0.0132

Gnomad AMR exome AF: 0.0172

Gnomad ASJ exome AF: 0.0199

Gnomad EAS exome AF: 0.0000586

Gnomad SAS exome AF: 0.0000334

Gnomad FIN exome AF: 0.0400

Gnomad NFE exome AF: 0.0791

Gnomad OTH exome AF: 0.0433

GnomAD4 exome AF: 0.0810 AC: 117282 AN: 1447224 Hom.: 6017 Cov.: 33 AF XY: 0.0778 AC XY: 56049 AN XY: 720750

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.0172

Gnomad4 ASJ exome AF: 0.0204

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.000129

Gnomad4 FIN exome AF: 0.0399

Gnomad4 NFE exome AF: 0.0991

Gnomad4 OTH exome AF: 0.0651

GnomAD4 genome AF: 0.0465 AC: 7082 AN: 152198 Hom.: 255 Cov.: 31 AF XY: 0.0422 AC XY: 3137 AN XY: 74404

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0243

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0386

Gnomad4 NFE AF: 0.0813

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0675 Hom.: 350

Bravo AF: 0.0442

TwinsUK AF: 0.121 AC: 447

ALSPAC AF: 0.107 AC: 413

ESP6500AA AF: 0.0179 AC: 79

ESP6500EA AF: 0.0815 AC: 701

ExAC AF: 0.0445 AC: 5407

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.0050
Dann	Benign	0.56
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0059	N
LIST_S2	Benign	0.32	T;T;T;T
MetaRNN	Benign	0.0023	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M;M;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.69	N;N;N;N
REVEL	Benign	0.015
Sift	Benign	0.11	T;T;T;T
Sift4G	Benign	0.24	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.070
MPC		0.080
ClinPred		0.0060	T
GERP RS		-1.3
Varity_R		0.023
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs41266839; hg19: chr6-26409890;