rs999171486

Variant names:

• chr5-181048112-G-C
• rs999171486
• NM_152547.5:c.295G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152547.5(BTNL9):​c.295G>C​(p.Ala99Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,613,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A99V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: BTNL9 NM_152547.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.778
• Publications: 0 publications found

Genes affected

BTNL9 (HGNC:24176): (butyrophilin like 9) Predicted to enable signaling receptor binding activity. Predicted to be involved in T cell receptor signaling pathway and regulation of cytokine production. Predicted to be located in plasma membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24833387).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152547.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL9	NM_152547.5	MANE Select	c.295G>C	p.Ala99Pro	missense	Exon 3 of 11	NP_689760.2	Q6UXG8-1
	BTNL9	NM_001308245.2		c.295G>C	p.Ala99Pro	missense	Exon 3 of 11	NP_001295174.1	Q6UXG8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL9	ENST00000327705.14	TSL:1 MANE Select	c.295G>C	p.Ala99Pro	missense	Exon 3 of 11	ENSP00000330200.9	Q6UXG8-1
	BTNL9	ENST00000376841.6	TSL:1	c.295G>C	p.Ala99Pro	missense	Exon 3 of 11	ENSP00000366037.2	Q6UXG8-3
	BTNL9	ENST00000864445.1		c.295G>C	p.Ala99Pro	missense	Exon 3 of 12	ENSP00000534504.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461308 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726952

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111970

Other (OTH) AF: 0.0000662 AC: 4 AN: 60386

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74358

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.000589 AC: 9 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000128

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.78
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.073
Sift	Benign	0.13	T
Sift4G	Benign	0.093	T
Polyphen		0.10	B
Vest4		0.26
MutPred		0.63		Gain of glycosylation at A99 (P = 0.0304)
MVP		0.37
MPC		0.47
ClinPred		0.32	T
GERP RS		3.2
Varity_R		0.20
gMVP		0.48
Mutation Taster		=88/12	polymorphism

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: rs999171486; hg19: chr5-180475112;