chr6-26448991-G-A

Variant names:

• chr6-26448991-G-A
• rs1796524
• NM_006994.5:c.964+237G>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.964+237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0856 in 151,946 control chromosomes in the GnomAD database, including 634 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 0.086 (634 hom., cov: 31)
• Consequence: BTN3A3 NM_006994.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 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.964+237G>A		intron	N/A	NP_008925.1
	BTN3A3	NM_197974.3		c.817+237G>A		intron	N/A	NP_932078.2
	BTN3A3	NM_001242803.2		c.334+237G>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.964+237G>A		intron	N/A	ENSP00000244519.2
	BTN3A3	ENST00000361232.7	TSL:2	c.817+237G>A		intron	N/A	ENSP00000355238.3
	BTN3A3	ENST00000490254.5	TSL:3	c.334+237G>A		intron	N/A	ENSP00000419736.1

Frequencies

GnomAD3 genomes AF: 0.0857 AC: 13006 AN: 151828 Hom.: 634 Cov.: 31

Gnomad AFR AF: 0.0536

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0796

Gnomad EAS AF: 0.0627

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.0949

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.100

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0856 AC: 13012 AN: 151946 Hom.: 634 Cov.: 31 AF XY: 0.0857 AC XY: 6366 AN XY: 74270

African (AFR) AF: 0.0535 AC: 2215 AN: 41434

American (AMR) AF: 0.0879 AC: 1341 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 276 AN: 3468

East Asian (EAS) AF: 0.0627 AC: 324 AN: 5168

South Asian (SAS) AF: 0.0569 AC: 274 AN: 4814

European-Finnish (FIN) AF: 0.0949 AC: 1002 AN: 10558

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7270 AN: 67934

Other (OTH) AF: 0.0996 AC: 210 AN: 2108

Alfa AF: 0.0940 Hom.: 353

Bravo AF: 0.0830

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.62
DANN	Benign	0.36
PhyloP100		-0.34
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: rs1796524; hg19: chr6-26449219;