6-26444504-C-T

Variant names:

• chr6-26444504-C-T
• rs9379875
• NM_006994.5:c.433+200C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

ENSG00000291336 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BTN3A3	NM_006994.5	c.433+200C>T		intron_variant	Intron 4 of 10	ENST00000244519.7	NP_008925.1
BTN3A3	NM_197974.3	c.307+200C>T		intron_variant	Intron 4 of 9		NP_932078.2
BTN3A3	NM_001242803.2	c.307+200C>T		intron_variant	Intron 2 of 5		NP_001229732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN3A3	ENST00000244519.7	c.433+200C>T		intron_variant	Intron 4 of 10	1	NM_006994.5	ENSP00000244519.2

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

African (AFR) AF: 0.0359 AC: 602 AN: 16766

American (AMR) AF: 0.0337 AC: 682 AN: 20214

Ashkenazi Jewish (ASJ) AF: 0.0393 AC: 601 AN: 15298

East Asian (EAS) AF: 0.133 AC: 4293 AN: 32312

South Asian (SAS) AF: 0.0910 AC: 4597 AN: 50530

European-Finnish (FIN) AF: 0.0818 AC: 2848 AN: 34796

Middle Eastern (MID) AF: 0.0495 AC: 123 AN: 2484

European-Non Finnish (NFE) AF: 0.114 AC: 55056 AN: 483244

Other (OTH) AF: 0.0896 AC: 3039 AN: 33930

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

African (AFR) AF: 0.0349 AC: 1448 AN: 41478

American (AMR) AF: 0.0378 AC: 579 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3470

East Asian (EAS) AF: 0.0998 AC: 517 AN: 5182

South Asian (SAS) AF: 0.0980 AC: 472 AN: 4818

European-Finnish (FIN) AF: 0.0769 AC: 814 AN: 10584

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7449 AN: 67996

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0930 Hom.: 347

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
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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