rs12214444

Variant names:

• chr6-26440424-C-T
• rs12214444
• ENST00000707189.1:n.1000-112763C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000707189.1(ENSG00000291336):​n.1000-112763C>T variant causes a intron 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: ENSG00000291336 ENST00000707189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000707189.1. 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
	BTN3A3	NM_006994.5	MANE Select	c.-291C>T		upstream_gene	N/A	NP_008925.1	O00478-1
	BTN3A3	NM_197974.3		c.-346C>T		upstream_gene	N/A	NP_932078.2	O00478-2
	BTN3A3	NM_001242803.2		c.-266C>T		upstream_gene	N/A	NP_001229732.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000291336	ENST00000707189.1		n.1000-112763C>T		intron	N/A
	ENSG00000291338	ENST00000707191.1		n.1001-92281C>T		intron	N/A
	BTN3A3	ENST00000244519.7	TSL:1 MANE Select	c.-291C>T		upstream_gene	N/A	ENSP00000244519.2	O00478-1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.124 AC: 5129 AN: 41504

American (AMR) AF: 0.140 AC: 2134 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 484 AN: 3470

East Asian (EAS) AF: 0.0304 AC: 158 AN: 5192

South Asian (SAS) AF: 0.158 AC: 762 AN: 4824

European-Finnish (FIN) AF: 0.126 AC: 1337 AN: 10588

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8210 AN: 68002

Other (OTH) AF: 0.110 AC: 233 AN: 2116

Alfa AF: 0.121 Hom.: 1713

Bravo AF: 0.123

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.67
PhyloP100		-1.4
PromoterAI		-0.16	Neutral

Splicing

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: rs12214444;

hg19: chr6-26440652;