rs41266839

Variant names:

• chr6-26409662-G-A
• rs41266839
• NM_007048.6:c.845G>A
• BTN3A1 p.Arg282Lys

Your query was ambiguous. Multiple possible variants found:

• chr6-26409662-G-A
• chr6-26409662-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007048.6(BTN3A1):​c.845G>A​(p.Arg282Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04733208).

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>A	p.Arg282Lys	missense	Exon 5 of 10	NP_008979.3
	BTN3A1	NM_001145008.2		c.689G>A	p.Arg230Lys	missense	Exon 5 of 10	NP_001138480.1	O00481-4
	BTN3A1	NM_001145009.2		c.845G>A	p.Arg282Lys	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>A	p.Arg282Lys	missense	Exon 5 of 10	ENSP00000289361.6	O00481-1
	BTN3A1	ENST00000476549.6	TSL:1	c.845G>A	p.Arg282Lys	missense	Exon 5 of 10	ENSP00000420010.2	O00481-2
	BTN3A1	ENST00000850859.1		c.845G>A	p.Arg282Lys	missense	Exon 5 of 10	ENSP00000520946.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1447296 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 720798

African (AFR) AF: 0.00 AC: 0 AN: 32032

American (AMR) AF: 0.00 AC: 0 AN: 39584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24992

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 85596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5620

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107454

Other (OTH) AF: 0.00 AC: 0 AN: 59460

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.0020
DANN	Benign	0.48
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0045	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.53	N
PhyloP100		-5.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.013
Sift	Benign	0.45	T
Sift4G	Benign	0.19	T
Varity_R		0.022
gMVP		0.098
Mutation Taster		=94/6	polymorphism

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;