rs3846845

Positions:

• chr6-26444687-G-A

Variant summary

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

The NM_006994.5(BTN3A3):​c.433+383G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 350,222 control chromosomes in the GnomAD database, including 41,794 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 0.53 (23450 hom., cov: 32)
  • Exomes 𝑓: 0.42 (18344 hom.)
• Consequence: BTN3A3 NM_006994.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

Genes affected

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTN3A3	NM_006994.5	c.433+383G>A		intron_variant		ENST00000244519.7	NP_008925.1
BTN3A3	NM_001242803.2	c.307+383G>A		intron_variant			NP_001229732.1
BTN3A3	NM_197974.3	c.307+383G>A		intron_variant			NP_932078.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTN3A3	ENST00000244519.7	c.433+383G>A		intron_variant		1	NM_006994.5	ENSP00000244519	P1
	ENST00000707189.1	n.1000-108500G>A		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1001-88018G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79792 AN: 152014 Hom.: 23405 Cov.: 32

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.418 AC: 82876 AN: 198088 Hom.: 18344 Cov.: 0 AF XY: 0.415 AC XY: 43499 AN XY: 104800

Gnomad4 AFR exome AF: 0.818

Gnomad4 AMR exome AF: 0.423

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.271

Gnomad4 SAS exome AF: 0.405

Gnomad4 FIN exome AF: 0.444

Gnomad4 NFE exome AF: 0.410

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.525 AC: 79888 AN: 152134 Hom.: 23450 Cov.: 32 AF XY: 0.521 AC XY: 38725 AN XY: 74354

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.481

Alfa AF: 0.480 Hom.: 2405

Bravo AF: 0.539

Asia WGS AF: 0.335 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs3846845; hg19: chr6-26444915;