chr5-181048118-C-T

Variant names:

• chr5-181048118-C-T
• rs376117622
• NM_152547.5:c.301C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152547.5(BTNL9):​c.301C>T​(p.Arg101Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,613,590 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000064 (0 hom.)
• Consequence: BTNL9 NM_152547.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.87
• Publications: 2 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.301C>T	p.Arg101Trp	missense	Exon 3 of 11	NP_689760.2	Q6UXG8-1
	BTNL9	NM_001308245.2		c.301C>T	p.Arg101Trp	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.301C>T	p.Arg101Trp	missense	Exon 3 of 11	ENSP00000330200.9	Q6UXG8-1
	BTNL9	ENST00000376841.6	TSL:1	c.301C>T	p.Arg101Trp	missense	Exon 3 of 11	ENSP00000366037.2	Q6UXG8-3
	BTNL9	ENST00000864445.1		c.301C>T	p.Arg101Trp	missense	Exon 3 of 12	ENSP00000534504.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 250148 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000643 AC: 94 AN: 1461274 Hom.: 0 Cov.: 31 AF XY: 0.0000647 AC XY: 47 AN XY: 726934

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52898

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

European-Non Finnish (NFE) AF: 0.0000701 AC: 78 AN: 1111968

Other (OTH) AF: 0.0000662 AC: 4 AN: 60382

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74484

African (AFR) AF: 0.000120 AC: 5 AN: 41562

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.0000264

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.099
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		1.9
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Benign	0.24
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.39
MVP		0.80
MPC		0.88
ClinPred		0.61	D
GERP RS		5.0
Varity_R		0.51
gMVP		0.30
Mutation Taster		=86/14	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: rs376117622; hg19: chr5-180475118; COSMIC: COSV59797072; COSMIC: COSV59797072;