chr5-180989061-C-G

Variant names:

• chr5-180989061-C-G
• rs79915597
• NM_197975.3:c.33C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_197975.3(BTNL3):​c.33C>G​(p.Phe11Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00386 in 1,448,098 control chromosomes in the GnomAD database, including 804 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (375 hom., cov: 24)
  • Exomes 𝑓: 0.0021 (429 hom.)
• Consequence: BTNL3 NM_197975.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.381
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025765002).
• BP6: Variant 5-180989061-C-G is Benign according to our data. Variant chr5-180989061-C-G is described in ClinVar as Benign. ClinVar VariationId is 781740.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

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.33C>G	p.Phe11Leu	missense	Exon 1 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.33C>G	p.Phe11Leu	missense	Exon 1 of 8	ENSP00000341787.6	Q6UXE8-1
	BTNL3	ENST00000899564.1		c.33C>G	p.Phe11Leu	missense	Exon 1 of 8	ENSP00000569623.1
	BTNL3	ENST00000946317.1		c.33C>G	p.Phe11Leu	missense	Exon 1 of 7	ENSP00000616376.1

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 2774 AN: 137558 Hom.: 375 Cov.: 24

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00794

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0132

Gnomad NFE AF: 0.000399

Gnomad OTH AF: 0.0190

GnomAD2 exomes AF: 0.00505 AC: 1048 AN: 207630 AF XY: 0.00356

Gnomad AFR exome AF: 0.0634

Gnomad AMR exome AF: 0.00355

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000331

Gnomad OTH exome AF: 0.00242

GnomAD4 exome AF: 0.00214 AC: 2804 AN: 1310436 Hom.: 429 Cov.: 30 AF XY: 0.00178 AC XY: 1164 AN XY: 652374

African (AFR) AF: 0.0669 AC: 2170 AN: 32450

American (AMR) AF: 0.00417 AC: 154 AN: 36898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24862

East Asian (EAS) AF: 0.00 AC: 0 AN: 35532

South Asian (SAS) AF: 0.0000967 AC: 8 AN: 82688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46688

Middle Eastern (MID) AF: 0.00204 AC: 11 AN: 5402

European-Non Finnish (NFE) AF: 0.000208 AC: 206 AN: 991050

Other (OTH) AF: 0.00465 AC: 255 AN: 54866

GnomAD4 genome AF: 0.0202 AC: 2780 AN: 137662 Hom.: 375 Cov.: 24 AF XY: 0.0188 AC XY: 1263 AN XY: 67078

African (AFR) AF: 0.0654 AC: 2611 AN: 39938

American (AMR) AF: 0.00793 AC: 104 AN: 13114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3338

East Asian (EAS) AF: 0.00 AC: 0 AN: 4648

South Asian (SAS) AF: 0.000216 AC: 1 AN: 4638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8922

Middle Eastern (MID) AF: 0.0142 AC: 4 AN: 282

European-Non Finnish (NFE) AF: 0.000399 AC: 24 AN: 60084

Other (OTH) AF: 0.0188 AC: 36 AN: 1918

Alfa AF: 0.0168 Hom.: 26

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0644 AC: 245

ESP6500EA AF: 0.000264 AC: 2

ExAC AF: 0.00596 AC: 665

Asia WGS AF: 0.00241 AC: 8 AN: 3328

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.19
DANN	Benign	0.25
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N
PhyloP100		-0.38
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.028
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.035
MutPred		0.40		Loss of helix (P = 0.1299)
MVP		0.24
MPC		0.46
ClinPred		0.0022	T
GERP RS		-0.27
PromoterAI		-0.0035	Neutral
Varity_R		0.039
gMVP		0.049
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs79915597; hg19: chr5-180416061;