6-26444504-C-T

Position:

• chr6-26444504-C-T

Variant summary

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

The NM_006994.5(BTN3A3):​c.433+200C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0993 in 841,722 control chromosomes in the GnomAD database, including 4,913 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 0.077 (564 hom., cov: 32)
  • Exomes 𝑓: 0.10 (4349 hom.)
• Consequence: BTN3A3 NM_006994.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTN3A3	NM_006994.5	c.433+200C>T		intron_variant		ENST00000244519.7
BTN3A3	NM_001242803.2	c.307+200C>T		intron_variant
BTN3A3	NM_197974.3	c.307+200C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTN3A3	ENST00000244519.7	c.433+200C>T		intron_variant		1	NM_006994.5	P1
	ENST00000707189.1	n.1000-108683C>T		intron_variant, non_coding_transcript_variant
	ENST00000707191.1	n.1001-88201C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11734 AN: 152030 Hom.: 565 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.0995

Gnomad SAS AF: 0.0989

Gnomad FIN AF: 0.0769

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0636

GnomAD4 exome AF: 0.104 AC: 71841 AN: 689574 Hom.: 4349 Cov.: 9 AF XY: 0.104 AC XY: 36560 AN XY: 351972

Gnomad4 AFR exome AF: 0.0359

Gnomad4 AMR exome AF: 0.0337

Gnomad4 ASJ exome AF: 0.0393

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.0910

Gnomad4 FIN exome AF: 0.0818

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.0896

GnomAD4 genome AF: 0.0771 AC: 11727 AN: 152148 Hom.: 564 Cov.: 32 AF XY: 0.0742 AC XY: 5523 AN XY: 74394

Gnomad4 AFR AF: 0.0349

Gnomad4 AMR AF: 0.0378

Gnomad4 ASJ AF: 0.0363

Gnomad4 EAS AF: 0.0998

Gnomad4 SAS AF: 0.0980

Gnomad4 FIN AF: 0.0769

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0953 Hom.: 282

Bravo AF: 0.0716

Asia WGS AF: 0.103 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.72

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: rs9379875; hg19: chr6-26444732; COSMIC: COSV55072691; COSMIC: COSV55072691;