chr6-26444687-G-A

Variant names:

• chr6-26444687-G-A
• rs3846845
• NM_006994.5:c.433+383G>A

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+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
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006994.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTN3A3	NM_006994.5	MANE Select	c.433+383G>A		intron	N/A	NP_008925.1
	BTN3A3	NM_197974.3		c.307+383G>A		intron	N/A	NP_932078.2
	BTN3A3	NM_001242803.2		c.307+383G>A		intron	N/A	NP_001229732.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTN3A3	ENST00000244519.7	TSL:1 MANE Select	c.433+383G>A		intron	N/A	ENSP00000244519.2
	BTN3A3	ENST00000480110.5	TSL:2	n.948G>A		non_coding_transcript_exon	Exon 3 of 7
	BTN3A3	ENST00000361232.7	TSL:2	c.307+383G>A		intron	N/A	ENSP00000355238.3

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

African (AFR) AF: 0.818 AC: 5415 AN: 6618

American (AMR) AF: 0.423 AC: 3165 AN: 7480

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 2274 AN: 5798

East Asian (EAS) AF: 0.271 AC: 2730 AN: 10072

South Asian (SAS) AF: 0.405 AC: 11331 AN: 28000

European-Finnish (FIN) AF: 0.444 AC: 4058 AN: 9132

Middle Eastern (MID) AF: 0.383 AC: 308 AN: 804

European-Non Finnish (NFE) AF: 0.410 AC: 48960 AN: 119356

Other (OTH) AF: 0.428 AC: 4635 AN: 10828

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

African (AFR) AF: 0.804 AC: 33409 AN: 41528

American (AMR) AF: 0.441 AC: 6747 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3468

East Asian (EAS) AF: 0.267 AC: 1381 AN: 5174

South Asian (SAS) AF: 0.406 AC: 1955 AN: 4816

European-Finnish (FIN) AF: 0.471 AC: 4973 AN: 10562

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28497 AN: 67980

Other (OTH) AF: 0.481 AC: 1015 AN: 2110

Alfa AF: 0.475 Hom.: 5044

Bravo AF: 0.539

Asia WGS AF: 0.335 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.56
PhyloP100		-0.39
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: rs3846845; hg19: chr6-26444915;