6-26409662-G-C

Variant names:

• chr6-26409662-G-C
• rs41266839
• NM_007048.6:c.845G>C
• BTN3A1 p.Arg282Thr

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 41 publications found

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]

ENSG00000291336 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007048.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTN3A1	NM_007048.6	MANE Select	c.845G>C	p.Arg282Thr	missense	Exon 5 of 10	NP_008979.3
	BTN3A1	NM_001145008.2		c.689G>C	p.Arg230Thr	missense	Exon 5 of 10	NP_001138480.1	O00481-4
	BTN3A1	NM_001145009.2		c.845G>C	p.Arg282Thr	missense	Exon 5 of 10	NP_001138481.1	O00481-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTN3A1	ENST00000289361.11	TSL:1 MANE Select	c.845G>C	p.Arg282Thr	missense	Exon 5 of 10	ENSP00000289361.6	O00481-1
	BTN3A1	ENST00000476549.6	TSL:1	c.845G>C	p.Arg282Thr	missense	Exon 5 of 10	ENSP00000420010.2	O00481-2
	BTN3A1	ENST00000850859.1		c.845G>C	p.Arg282Thr	missense	Exon 5 of 10	ENSP00000520946.1

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

GnomAD2 exomes AF: 0.0446 AC: 10575 AN: 236930 AF XY: 0.0443

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 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

African (AFR) AF: 0.0116 AC: 370 AN: 32030

American (AMR) AF: 0.0172 AC: 681 AN: 39580

Ashkenazi Jewish (ASJ) AF: 0.0204 AC: 511 AN: 24992

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39642

South Asian (SAS) AF: 0.000129 AC: 11 AN: 85596

European-Finnish (FIN) AF: 0.0399 AC: 2109 AN: 52908

Middle Eastern (MID) AF: 0.00320 AC: 18 AN: 5620

European-Non Finnish (NFE) AF: 0.0991 AC: 109708 AN: 1107398

Other (OTH) AF: 0.0651 AC: 3871 AN: 59458

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

African (AFR) AF: 0.0129 AC: 534 AN: 41540

American (AMR) AF: 0.0243 AC: 371 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.0386 AC: 410 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0813 AC: 5524 AN: 67976

Other (OTH) AF: 0.0327 AC: 69 AN: 2112

Alfa AF: 0.0675 Hom.: 350

Bravo AF: 0.0442

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0059	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		-5.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.015
Sift	Benign	0.11	T
Sift4G	Benign	0.24	T
Varity_R		0.023
gMVP		0.12
Mutation Taster		=98/2	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41266839;

hg19: chr6-26409890;

COSMIC: COSV107231553;

COSMIC: COSV107231553;