rs12214444

Positions:

• chr6-26440424-C-T

Variant summary

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

The ENST00000707189.1(ENSG00000291336):​n.1000-112763C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,182 control chromosomes in the GnomAD database, including 1,199 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 (1199 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENST00000707189.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

Genes affected

(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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000707189.1	n.1000-112763C>T		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1001-92281C>T		intron_variant, non_coding_transcript_variant
BTN3A3	ENST00000482451.5			upstream_gene_variant		5		ENSP00000419312
BTN3A3	ENST00000494393.5			upstream_gene_variant		4		ENSP00000417234

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18627 AN: 152064 Hom.: 1194 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.111

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.123 AC: 18654 AN: 152182 Hom.: 1199 Cov.: 33 AF XY: 0.123 AC XY: 9148 AN XY: 74414

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.0304

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.110

Alfa AF: 0.120 Hom.: 1090

Bravo AF: 0.123

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12214444; hg19: chr6-26440652;