5-181045584-G-C

Variant names:

• chr5-181045584-G-C
• rs1283203924
• NM_152547.5:c.95G>C

Variant summary

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

The NM_152547.5(BTNL9):​c.95G>C​(p.Gly32Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G32E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BTNL9 NM_152547.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06225887).

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.95G>C	p.Gly32Ala	missense	Exon 2 of 11	NP_689760.2	Q6UXG8-1
	BTNL9	NM_001308245.2		c.95G>C	p.Gly32Ala	missense	Exon 2 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.95G>C	p.Gly32Ala	missense	Exon 2 of 11	ENSP00000330200.9	Q6UXG8-1
	BTNL9	ENST00000376841.6	TSL:1	c.95G>C	p.Gly32Ala	missense	Exon 2 of 11	ENSP00000366037.2	Q6UXG8-3
	BTNL9	ENST00000864445.1		c.95G>C	p.Gly32Ala	missense	Exon 2 of 12	ENSP00000534504.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459930 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726338

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110986

Other (OTH) AF: 0.00 AC: 0 AN: 60314

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.2
DANN	Benign	0.85
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N
PhyloP100		-0.38
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.020
Sift	Benign	1.0	T
Sift4G	Benign	0.85	T
Polyphen		0.45	P
Vest4		0.12
MutPred		0.28		Gain of sheet (P = 0.0125)
MVP		0.33
MPC		0.71
ClinPred		0.12	T
GERP RS		-1.4
Varity_R		0.031
gMVP		0.16
Mutation Taster		=92/8	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: rs1283203924; hg19: chr5-180472584;