6-26409554-A-G

Variant names:

• chr6-26409554-A-G
• rs145059723
• NM_007048.6:c.737A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007048.6(BTN3A1):​c.737A>G​(p.Gln246Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000946 in 1,613,742 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00055 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00099 (1 hom.)
• Consequence: BTN3A1 NM_007048.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.511
• Publications: 3 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014321595).

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.737A>G	p.Gln246Arg	missense	Exon 5 of 10	NP_008979.3
	BTN3A1	NM_001145008.2		c.581A>G	p.Gln194Arg	missense	Exon 5 of 10	NP_001138480.1	O00481-4
	BTN3A1	NM_001145009.2		c.737A>G	p.Gln246Arg	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.737A>G	p.Gln246Arg	missense	Exon 5 of 10	ENSP00000289361.6	O00481-1
	BTN3A1	ENST00000476549.6	TSL:1	c.737A>G	p.Gln246Arg	missense	Exon 5 of 10	ENSP00000420010.2	O00481-2
	BTN3A1	ENST00000850859.1		c.737A>G	p.Gln246Arg	missense	Exon 5 of 10	ENSP00000520946.1

Frequencies

GnomAD3 genomes AF: 0.000553 AC: 84 AN: 151844 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000566 AC: 142 AN: 251074 AF XY: 0.000611

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000986 AC: 1442 AN: 1461780 Hom.: 1 Cov.: 32 AF XY: 0.000919 AC XY: 668 AN XY: 727192

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00126 AC: 1398 AN: 1112000

Other (OTH) AF: 0.000596 AC: 36 AN: 60376

GnomAD4 genome AF: 0.000553 AC: 84 AN: 151962 Hom.: 0 Cov.: 31 AF XY: 0.000390 AC XY: 29 AN XY: 74288

African (AFR) AF: 0.000265 AC: 11 AN: 41446

American (AMR) AF: 0.000131 AC: 2 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000918 Hom.: 0

Bravo AF: 0.000608

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000642 AC: 78

EpiCase AF: 0.000818

EpiControl AF: 0.00142

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.54
DANN	Benign	0.85
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.49	N
PhyloP100		-0.51
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.013
Sift	Benign	0.039	D
Sift4G	Benign	0.55	T
Polyphen		0.024	B
Vest4		0.16
MVP		0.27
MPC		0.061
ClinPred		0.0099	T
GERP RS		-0.10
Varity_R		0.029
gMVP		0.087
Mutation Taster		=95/5	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

Other links and lift over

dbSNP: rs145059723; hg19: chr6-26409782;