rs9379875

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-26444504-C-A
• chr6-26444504-C-G
• chr6-26444504-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006994.5(BTN3A3):​c.433+200C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 690,144 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BTN3A3 NM_006994.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTN3A3	NM_006994.5	c.433+200C>A		intron_variant	Intron 4 of 10	ENST00000244519.7	NP_008925.1
BTN3A3	NM_197974.3	c.307+200C>A		intron_variant	Intron 4 of 9		NP_932078.2
BTN3A3	NM_001242803.2	c.307+200C>A		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>A		intron_variant	Intron 4 of 10	1	NM_006994.5	ENSP00000244519.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000145 AC: 1 AN: 690144 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 352260

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16768

American (AMR) AF: 0.00 AC: 0 AN: 20214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15298

East Asian (EAS) AF: 0.00 AC: 0 AN: 32324

South Asian (SAS) AF: 0.00 AC: 0 AN: 50538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2484

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 483768

Other (OTH) AF: 0.0000295 AC: 1 AN: 33940

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.67
DANN	Benign	0.70
PhyloP100		-0.93

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;