17-43848758-C-T

Variant names:

• chr17-43848758-C-T
• rs72836561
• NM_145273.4:c.244C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_145273.4(CD300LG):​c.244C>T​(p.Arg82Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 1,614,084 control chromosomes in the GnomAD database, including 700 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.020 (41 hom., cov: 32)
  • Exomes 𝑓: 0.028 (659 hom.)
• Consequence: CD300LG NM_145273.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 46 publications found

Genes affected

CD300LG (HGNC:30455): (CD300 molecule like family member g) Members of the CD300 (see MIM 606786)-like (CD300L) family, such as CD300LG, are widely expressed on hematopoietic cells. All CD300L proteins are type I cell surface glycoproteins that contain a single immunoglobulin (Ig) V-like domain (Takatsu et al., 2006 [PubMed 16876123]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014021635).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0203 (3089/152240) while in subpopulation NFE AF = 0.0309 (2102/68012). AF 95% confidence interval is 0.0298. There are 41 homozygotes in GnomAd4. There are 1472 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145273.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD300LG	NM_145273.4	MANE Select	c.244C>T	p.Arg82Cys	missense	Exon 2 of 7	NP_660316.2
	CD300LG	NM_001168322.2		c.244C>T	p.Arg82Cys	missense	Exon 2 of 7	NP_001161794.1
	CD300LG	NM_001168323.2		c.244C>T	p.Arg82Cys	missense	Exon 2 of 6	NP_001161795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD300LG	ENST00000317310.5	TSL:1 MANE Select	c.244C>T	p.Arg82Cys	missense	Exon 2 of 7	ENSP00000321005.3
	CD300LG	ENST00000539718.5	TSL:1	c.244C>T	p.Arg82Cys	missense	Exon 2 of 7	ENSP00000442368.1
	CD300LG	ENST00000293396.12	TSL:1	c.244C>T	p.Arg82Cys	missense	Exon 2 of 6	ENSP00000293396.7

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 3092 AN: 152122 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.00534

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.0219 AC: 5498 AN: 251414 AF XY: 0.0223

Gnomad AFR exome AF: 0.00523

Gnomad AMR exome AF: 0.00942

Gnomad ASJ exome AF: 0.0101

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0287

Gnomad NFE exome AF: 0.0308

Gnomad OTH exome AF: 0.0194

GnomAD4 exome AF: 0.0277 AC: 40424 AN: 1461844 Hom.: 659 Cov.: 31 AF XY: 0.0274 AC XY: 19921 AN XY: 727218

African (AFR) AF: 0.00451 AC: 151 AN: 33476

American (AMR) AF: 0.0101 AC: 453 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00983 AC: 257 AN: 26136

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39700

South Asian (SAS) AF: 0.0235 AC: 2025 AN: 86258

European-Finnish (FIN) AF: 0.0314 AC: 1675 AN: 53388

Middle Eastern (MID) AF: 0.00693 AC: 40 AN: 5768

European-Non Finnish (NFE) AF: 0.0310 AC: 34522 AN: 1112002

Other (OTH) AF: 0.0214 AC: 1293 AN: 60392

GnomAD4 genome AF: 0.0203 AC: 3089 AN: 152240 Hom.: 41 Cov.: 32 AF XY: 0.0198 AC XY: 1472 AN XY: 74432

African (AFR) AF: 0.00532 AC: 221 AN: 41538

American (AMR) AF: 0.0167 AC: 255 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4810

European-Finnish (FIN) AF: 0.0299 AC: 318 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0309 AC: 2102 AN: 68012

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.0263 Hom.: 227

Bravo AF: 0.0179

TwinsUK AF: 0.0305 AC: 113

ALSPAC AF: 0.0283 AC: 109

ESP6500AA AF: 0.00658 AC: 29

ESP6500EA AF: 0.0303 AC: 261

ExAC AF: 0.0225 AC: 2733

Asia WGS AF: 0.0110 AC: 40 AN: 3478

EpiCase AF: 0.0248

EpiControl AF: 0.0236

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.085
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.28
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.049
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.066
MPC		0.055
ClinPred		0.065	T
GERP RS		1.1
Varity_R		0.32
gMVP		0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs72836561; hg19: chr17-41926126; COSMIC: COSV107354906;