6-26441412-C-T

Variant names:

• chr6-26441412-C-T
• rs13220495
• NM_006994.5:c.-67+764C>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.-67+764C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 151,742 control chromosomes in the GnomAD database, including 274 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 0.052 (274 hom., cov: 32)
• Consequence: BTN3A3 NM_006994.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• Publications: 26 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN3A3	NM_006994.5	c.-67+764C>T		intron_variant	Intron 1 of 10	ENST00000244519.7	NP_008925.1
BTN3A3	NM_197974.3	c.-122+764C>T		intron_variant	Intron 1 of 9		NP_932078.2
BTN3A3	NM_001242803.2	c.-42+764C>T		intron_variant	Intron 1 of 5		NP_001229732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTN3A3	ENST00000244519.7	c.-67+764C>T		intron_variant	Intron 1 of 10	1	NM_006994.5	ENSP00000244519.2

Frequencies

GnomAD3 genomes AF: 0.0516 AC: 7818 AN: 151638 Hom.: 274 Cov.: 32

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.0360

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

GnomAD4 genome AF: 0.0515 AC: 7815 AN: 151742 Hom.: 274 Cov.: 32 AF XY: 0.0468 AC XY: 3469 AN XY: 74132

African (AFR) AF: 0.0289 AC: 1198 AN: 41396

American (AMR) AF: 0.0252 AC: 385 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.0392 AC: 407 AN: 10386

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.0821 AC: 5575 AN: 67936

Other (OTH) AF: 0.0357 AC: 75 AN: 2100

Alfa AF: 0.0791 Hom.: 299

Bravo AF: 0.0499

Asia WGS AF: 0.00521 AC: 19 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.35
DANN	Benign	0.21
PhyloP100		-0.45
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: rs13220495; hg19: chr6-26441640;