17-74695789-T-C

Variant names:

• chr17-74695789-T-C
• rs2034310
• NM_139018.5:c.653A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139018.5(CD300LF):​c.653A>G​(p.Gln218Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 1,613,910 control chromosomes in the GnomAD database, including 511,975 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.75 (42789 hom., cov: 33)
  • Exomes 𝑓: 0.80 (469186 hom.)
• Consequence: CD300LF NM_139018.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 55 publications found

Genes affected

CD300LF (HGNC:29883): (CD300 molecule like family member f) This gene encodes a member of the CD300 protein family. Members of this family are cell surface glycoproteins with a single IgV-like extracellular domain, and are involved in the regulation of immune response. The encoded protein is an inhibitory receptor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

RAB37 (HGNC:30268): (RAB37, member RAS oncogene family) Rab proteins are low molecular mass GTPases that are critical regulators of vesicle trafficking. For additional background information on Rab proteins, see MIM 179508.[supplied by OMIM, Apr 2006]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=7.582666E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD300LF	NM_139018.5	c.653A>G	p.Gln218Arg	missense_variant	Exon 6 of 7	ENST00000326165.11	NP_620587.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD300LF	ENST00000326165.11	c.653A>G	p.Gln218Arg	missense_variant	Exon 6 of 7	1	NM_139018.5	ENSP00000327075.6

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113298 AN: 151994 Hom.: 42762 Cov.: 33

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.772

GnomAD2 exomes AF: 0.773 AC: 194065 AN: 251198 AF XY: 0.782

Gnomad AFR exome AF: 0.623

Gnomad AMR exome AF: 0.700

Gnomad ASJ exome AF: 0.885

Gnomad EAS exome AF: 0.673

Gnomad FIN exome AF: 0.774

Gnomad NFE exome AF: 0.818

Gnomad OTH exome AF: 0.789

GnomAD4 exome AF: 0.800 AC: 1168717 AN: 1461798 Hom.: 469186 Cov.: 65 AF XY: 0.801 AC XY: 582395 AN XY: 727194

African (AFR) AF: 0.627 AC: 20977 AN: 33480

American (AMR) AF: 0.700 AC: 31294 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 23036 AN: 26136

East Asian (EAS) AF: 0.666 AC: 26451 AN: 39694

South Asian (SAS) AF: 0.788 AC: 67930 AN: 86258

European-Finnish (FIN) AF: 0.772 AC: 41240 AN: 53388

Middle Eastern (MID) AF: 0.856 AC: 4937 AN: 5766

European-Non Finnish (NFE) AF: 0.814 AC: 905078 AN: 1111974

Other (OTH) AF: 0.791 AC: 47774 AN: 60394

GnomAD4 genome AF: 0.745 AC: 113363 AN: 152112 Hom.: 42789 Cov.: 33 AF XY: 0.743 AC XY: 55223 AN XY: 74330

African (AFR) AF: 0.631 AC: 26172 AN: 41478

American (AMR) AF: 0.705 AC: 10785 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 3025 AN: 3472

East Asian (EAS) AF: 0.652 AC: 3357 AN: 5152

South Asian (SAS) AF: 0.778 AC: 3755 AN: 4824

European-Finnish (FIN) AF: 0.773 AC: 8188 AN: 10596

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55441 AN: 67982

Other (OTH) AF: 0.767 AC: 1622 AN: 2114

Alfa AF: 0.796 Hom.: 171035

Bravo AF: 0.738

TwinsUK AF: 0.802 AC: 2973

ALSPAC AF: 0.810 AC: 3121

ESP6500AA AF: 0.641 AC: 2824

ESP6500EA AF: 0.815 AC: 7007

ExAC AF: 0.773 AC: 93861

Asia WGS AF: 0.685 AC: 2382 AN: 3478

EpiCase AF: 0.832

EpiControl AF: 0.833

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.76
DANN	Benign	0.55
DEOGEN2	Benign	0.038	T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.22	T;T;T
MetaRNN	Benign	7.6e-7	T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.16
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.37	N;.;.
REVEL	Benign	0.012
Sift	Benign	0.92	T;.;.
Sift4G	Benign	0.52	T;T;T
Polyphen		0.0010	B;.;B
Vest4		0.046
MPC		0.11
ClinPred		0.0014	T
GERP RS		-0.60
Varity_R		0.023
gMVP		0.066
Mutation Taster		=100/0	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: rs2034310; hg19: chr17-72691928; COSMIC: COSV56896307;