17-74525957-C-G

Variant names:

• chr17-74525957-C-G
• rs150773470
• NM_174892.4:c.161G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174892.4(CD300LB):​c.161G>C​(p.Arg54Pro) 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 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. R54H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CD300LB NM_174892.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.70
• Publications: 0 publications found

Genes affected

CD300LB (HGNC:30811): (CD300 molecule like family member b) CD300LB is a nonclassical activating receptor of the immunoglobulin (Ig) superfamily expressed on myeloid cells (Martinez-Barriocanal and Sayos, 2006 [PubMed 16920917]).[supplied by OMIM, Mar 2008]

ENSG00000289070 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09061605).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174892.4. 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
	CD300LB	NM_174892.4	MANE Select	c.161G>C	p.Arg54Pro	missense	Exon 2 of 4	NP_777552.3	A8K4G0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD300LB	ENST00000392621.6	TSL:1 MANE Select	c.161G>C	p.Arg54Pro	missense	Exon 2 of 4	ENSP00000376397.2	A8K4G0
	CD300LB	ENST00000718280.1		c.161G>C	p.Arg54Pro	missense	Exon 2 of 4	ENSP00000520719.1	A8K4G0
	CD300LB	ENST00000314401.3	TSL:2	c.161G>C	p.Arg54Pro	missense	Exon 2 of 3	ENSP00000317337.4	J9JID3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251454 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461880 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.0010
DANN	Benign	0.36
DEOGEN2	Benign	0.082	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.0099	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-7.7
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.061
Sift	Benign	0.29	T
Sift4G	Benign	0.28	T
Polyphen		0.0030	B
Vest4		0.25
MutPred		0.43		Loss of MoRF binding (P = 0.0089)
MVP		0.20
MPC		0.38
ClinPred		0.15	T
GERP RS		-10
Varity_R		0.11
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs150773470; hg19: chr17-72522096;