6-26453514-A-G

Variant names:

• chr6-26453514-A-G
• rs10484440
• ENST00000707189.1:n.1000-99673A>G

Variant summary

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

The ENST00000707189.1(ENSG00000291336):​n.1000-99673A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 151,920 control chromosomes in the GnomAD database, including 1,252 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1251 hom., cov: 31)
  • Exomes 𝑓: 0.17 (1 hom.)
• Consequence: ENSG00000291336 ENST00000707189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

Genes affected

ENSG00000291336 (HGNC:):

BTN3A3 (HGNC:1140): (butyrophilin subfamily 3 member A3) 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., BNT3A3) 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN3A3	NM_006994.5	c.*1103A>G		downstream_gene_variant		ENST00000244519.7	NP_008925.1
BTN3A3	NM_197974.3	c.*1103A>G		downstream_gene_variant			NP_932078.2
BTN3A3	NM_001242803.2	c.*1103A>G		downstream_gene_variant			NP_001229732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000291336	ENST00000707189.1	n.1000-99673A>G		intron_variant	Intron 1 of 1
ENSG00000291338	ENST00000707191.1	n.1001-79191A>G		intron_variant	Intron 1 of 1
BTN3A3	ENST00000244519.7	c.*1103A>G		downstream_gene_variant		1	NM_006994.5	ENSP00000244519.2
BTN3A3	ENST00000480110.5	n.*100A>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18938 AN: 151780 Hom.: 1251 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0904

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.0437

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.167 AC: 4 AN: 24 Hom.: 1 AF XY: 0.167 AC XY: 3 AN XY: 18

Gnomad4 AFR exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.125 AC: 18945 AN: 151896 Hom.: 1251 Cov.: 31 AF XY: 0.127 AC XY: 9426 AN XY: 74214

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0904

Gnomad4 EAS AF: 0.0773

Gnomad4 SAS AF: 0.0433

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.117

Alfa AF: 0.121 Hom.: 1251

Bravo AF: 0.119

Asia WGS AF: 0.0460 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10484440; hg19: chr6-26453742;