chr17-74582311-C-T

Variant names:

• chr17-74582311-C-T
• rs968352745
• NM_001115152.2:c.380G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001115152.2(CD300LD):​c.380G>A​(p.Gly127Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CD300LD NM_001115152.2 missense, splice_region
• Scores: Splicing: ADA: 0.001690
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.41
• Publications: 0 publications found

Genes affected

CD300LD (HGNC:16848): (CD300 molecule like family member d) Predicted to enable transmembrane signaling receptor activity and virus receptor activity. Predicted to be involved in immune system process. Predicted to act upstream of or within regulation of interleukin-6 production and regulation of tumor necrosis factor production. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040180206).
• BP6: Variant 17-74582311-C-T is Benign according to our data. Variant chr17-74582311-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3140527.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001115152.2. 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
	CD300LD	NM_001115152.2	MANE Select	c.380G>A	p.Gly127Asp	missense splice_region	Exon 3 of 4	NP_001108624.1	Q6UXZ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD300LD	ENST00000375352.1	TSL:1 MANE Select	c.380G>A	p.Gly127Asp	missense splice_region	Exon 3 of 4	ENSP00000364501.1	Q6UXZ3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 248804 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000871

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: 0.000165

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460592 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726688

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.0000671 AC: 3 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111036

Other (OTH) AF: 0.0000166 AC: 1 AN: 60336

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41416

American (AMR) AF: 0.000131 AC: 2 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.087
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.11
DANN	Benign	0.48
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00027	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
PhyloP100		-3.4
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.0080
Sift	Benign	0.16	T
Sift4G	Benign	0.086	T
Polyphen		0.014	B
Vest4		0.060
MutPred		0.49		Gain of solvent accessibility (P = 0.0648)
MVP		0.067
MPC		0.051
ClinPred		0.031	T
GERP RS		-3.8
Varity_R		0.057
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0017
dbscSNV1_RF	Benign	0.10
SpliceAI score (max)		0.080		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: rs968352745; hg19: chr17-72578450;