rs148701737

Variant names:

• chr5-180993151-C-T
• rs148701737
• NM_197975.3:c.388C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_197975.3(BTNL3):​c.388C>T​(p.Arg130Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,436,386 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R130Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00060 (19 hom., cov: 24)
  • Exomes 𝑓: 0.00079 (162 hom.)
• Consequence: BTNL3 NM_197975.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.73
• Publications: 1 publications found

Genes affected

BTNL3 (HGNC:1143): (butyrophilin like 3) 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 integral component of membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299843 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011764735).
• BP6: Variant 5-180993151-C-T is Benign according to our data. Variant chr5-180993151-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 738102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197975.3. 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
	BTNL3	NM_197975.3	MANE Select	c.388C>T	p.Arg130Trp	missense	Exon 2 of 8	NP_932079.1	Q6UXE8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTNL3	ENST00000342868.7	TSL:1 MANE Select	c.388C>T	p.Arg130Trp	missense	Exon 2 of 8	ENSP00000341787.6	Q6UXE8-1
	BTNL3	ENST00000899564.1		c.388C>T	p.Arg130Trp	missense	Exon 2 of 8	ENSP00000569623.1
	BTNL3	ENST00000946317.1		c.50-4062C>T		intron	N/A	ENSP00000616376.1

Frequencies

GnomAD3 genomes AF: 0.000601 AC: 82 AN: 136438 Hom.: 19 Cov.: 24

Gnomad AFR AF: 0.0000504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00155

Gnomad ASJ AF: 0.000602

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00742

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00331

Gnomad NFE AF: 0.000352

Gnomad OTH AF: 0.00106

GnomAD2 exomes AF: 0.00140 AC: 256 AN: 183420 AF XY: 0.00159

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000382

Gnomad ASJ exome AF: 0.00114

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000361

Gnomad OTH exome AF: 0.00301

GnomAD4 exome AF: 0.000792 AC: 1029 AN: 1299842 Hom.: 162 Cov.: 31 AF XY: 0.00100 AC XY: 647 AN XY: 645414

African (AFR) AF: 0.000154 AC: 5 AN: 32464

American (AMR) AF: 0.000360 AC: 13 AN: 36100

Ashkenazi Jewish (ASJ) AF: 0.00159 AC: 39 AN: 24592

East Asian (EAS) AF: 0.0000570 AC: 2 AN: 35102

South Asian (SAS) AF: 0.00693 AC: 565 AN: 81480

European-Finnish (FIN) AF: 0.0000220 AC: 1 AN: 45430

Middle Eastern (MID) AF: 0.00589 AC: 31 AN: 5260

European-Non Finnish (NFE) AF: 0.000266 AC: 262 AN: 984906

Other (OTH) AF: 0.00204 AC: 111 AN: 54508

GnomAD4 genome AF: 0.000601 AC: 82 AN: 136544 Hom.: 19 Cov.: 24 AF XY: 0.000633 AC XY: 42 AN XY: 66390

African (AFR) AF: 0.0000503 AC: 2 AN: 39766

American (AMR) AF: 0.00155 AC: 20 AN: 12900

Ashkenazi Jewish (ASJ) AF: 0.000602 AC: 2 AN: 3322

East Asian (EAS) AF: 0.00 AC: 0 AN: 4656

South Asian (SAS) AF: 0.00744 AC: 34 AN: 4572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8752

Middle Eastern (MID) AF: 0.00355 AC: 1 AN: 282

European-Non Finnish (NFE) AF: 0.000352 AC: 21 AN: 59602

Other (OTH) AF: 0.00105 AC: 2 AN: 1908

Alfa AF: 0.000572 Hom.: 1

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00127 AC: 140

Asia WGS AF: 0.00543 AC: 18 AN: 3326

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.085	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.7
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.013	D
Polyphen		0.96	D
Vest4		0.16
MVP		0.21
MPC		0.92
ClinPred		0.15	T
GERP RS		-5.8
Varity_R		0.12
gMVP		0.21
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs148701737; hg19: chr5-180420151;