17-49510457-C-T

Variant names:

• chr17-49510457-C-T
• rs2072446
• NM_002507.4:c.614C>T

Variant summary

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

The NM_002507.4(NGFR):​c.614C>T​(p.Ser205Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0493 in 1,614,018 control chromosomes in the GnomAD database, including 2,211 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.042 (190 hom., cov: 32)
  • Exomes 𝑓: 0.050 (2021 hom.)
• Consequence: NGFR NM_002507.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 70 publications found

Genes affected

NGFR (HGNC:7809): (nerve growth factor receptor) Nerve growth factor receptor contains an extracellular domain containing four 40-amino acid repeats with 6 cysteine residues at conserved positions followed by a serine/threonine-rich region, a single transmembrane domain, and a 155-amino acid cytoplasmic domain. The cysteine-rich region contains the nerve growth factor binding domain. [provided by RefSeq, Jul 2008]

NGFR-AS1 (HGNC:55555): (NGFR antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019932091).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002507.4. 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
	NGFR	NM_002507.4	MANE Select	c.614C>T	p.Ser205Leu	missense	Exon 4 of 6	NP_002498.1	P08138-1
	NGFR-AS1	NR_103773.1		n.377+526G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	ENST00000172229.8	TSL:1 MANE Select	c.614C>T	p.Ser205Leu	missense	Exon 4 of 6	ENSP00000172229.3	P08138-1
	NGFR	ENST00000504201.1	TSL:2	c.332C>T	p.Ser111Leu	missense	Exon 4 of 6	ENSP00000421731.1	P08138-2
	NGFR-AS1	ENST00000514506.1	TSL:2	n.377+526G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6404 AN: 152098 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0612

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.0575

GnomAD2 exomes AF: 0.0519 AC: 13020 AN: 251074 AF XY: 0.0535

Gnomad AFR exome AF: 0.0114

Gnomad AMR exome AF: 0.0372

Gnomad ASJ exome AF: 0.0525

Gnomad EAS exome AF: 0.109

Gnomad FIN exome AF: 0.0510

Gnomad NFE exome AF: 0.0508

Gnomad OTH exome AF: 0.0549

GnomAD4 exome AF: 0.0501 AC: 73229 AN: 1461802 Hom.: 2021 Cov.: 32 AF XY: 0.0506 AC XY: 36762 AN XY: 727202

African (AFR) AF: 0.0114 AC: 380 AN: 33476

American (AMR) AF: 0.0390 AC: 1743 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0498 AC: 1301 AN: 26130

East Asian (EAS) AF: 0.107 AC: 4261 AN: 39700

South Asian (SAS) AF: 0.0587 AC: 5063 AN: 86254

European-Finnish (FIN) AF: 0.0494 AC: 2635 AN: 53374

Middle Eastern (MID) AF: 0.0465 AC: 268 AN: 5768

European-Non Finnish (NFE) AF: 0.0489 AC: 54321 AN: 1111992

Other (OTH) AF: 0.0539 AC: 3257 AN: 60388

GnomAD4 genome AF: 0.0421 AC: 6406 AN: 152216 Hom.: 190 Cov.: 32 AF XY: 0.0431 AC XY: 3208 AN XY: 74428

African (AFR) AF: 0.0135 AC: 560 AN: 41530

American (AMR) AF: 0.0532 AC: 814 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0502 AC: 174 AN: 3466

East Asian (EAS) AF: 0.110 AC: 570 AN: 5162

South Asian (SAS) AF: 0.0608 AC: 293 AN: 4818

European-Finnish (FIN) AF: 0.0516 AC: 548 AN: 10610

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0485 AC: 3297 AN: 68012

Other (OTH) AF: 0.0573 AC: 121 AN: 2110

Alfa AF: 0.0477 Hom.: 394

Bravo AF: 0.0422

TwinsUK AF: 0.0467 AC: 173

ALSPAC AF: 0.0475 AC: 183

ESP6500AA AF: 0.0132 AC: 58

ESP6500EA AF: 0.0509 AC: 438

ExAC AF: 0.0512 AC: 6218

Asia WGS AF: 0.0740 AC: 258 AN: 3478

EpiCase AF: 0.0543

EpiControl AF: 0.0558

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.22
Sift	Benign	0.26	T
Sift4G	Benign	0.11	T
Polyphen		0.0080	B
Vest4		0.16
MPC		0.49
ClinPred		0.013	T
GERP RS		4.7
Varity_R		0.063
gMVP		0.50
Mutation Taster		=81/19	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: rs2072446; hg19: chr17-47587819; COSMIC: COSV50803302; COSMIC: COSV50803302;