Genetic Variant NGFR:p.Ser205Leu (chr17-49510457-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.042 ( 190 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2021 hom. )

Consequence

NGFR
NM_002507.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

Variant links:

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 links:

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

NGFR-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGFR	NM_002507.4 link	c.614C>T	p.Ser205Leu	missense_variant	Exon 4 of 6	ENST00000172229.8	NP_002498.1	P08138-1
NGFR-AS1	NR_103773.1 link	n.377+526G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NGFR	ENST00000172229.8 link	c.614C>T	p.Ser205Leu	missense_variant	Exon 4 of 6	1	NM_002507.4	ENSP00000172229.3	P08138-1
NGFR	ENST00000504201.1 link	c.332C>T	p.Ser111Leu	missense_variant	Exon 4 of 6	2		ENSP00000421731.1	P08138-2
NGFR-AS1	ENST00000514506.1 link	n.377+526G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0421

AC:

6404

AN:

152098

Hom.:

189

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0519

AC:

13020

AN:

251074

Hom.:

442

AF XY:

0.0535

AC XY:

7259

AN XY:

135750

show subpopulations

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 SAS exome

AF:

0.0591

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.:

AF XY:

0.0506

AC XY:

36762

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.0114

Gnomad4 AMR exome

AF:

0.0390

Gnomad4 ASJ exome

AF:

0.0498

Gnomad4 EAS exome

AF:

0.107

Gnomad4 SAS exome

AF:

0.0587

Gnomad4 FIN exome

AF:

0.0494

Gnomad4 NFE exome

AF:

0.0489

Gnomad4 OTH exome

AF:

0.0539

GnomAD4 genome

AF:

0.0421

AC:

6406

AN:

152216

Hom.:

190

Cov.:

AF XY:

0.0431

AC XY:

3208

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0135

Gnomad4 AMR

AF:

0.0532

Gnomad4 ASJ

AF:

0.0502

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.0608

Gnomad4 FIN

AF:

0.0516

Gnomad4 NFE

AF:

0.0485

Gnomad4 OTH

AF:

0.0573

Alfa

AF:

0.0506

Hom.:

323

Bravo

AF:

0.0422

TwinsUK

AF:

0.0467

AC:

173

ALSPAC

AF:

0.0475

AC:

183

ESP6500AA

AF:

0.0132

AC:

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.35

T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.84

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.9

L;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.94

N;N

REVEL

Benign

0.22

Sift

Benign

0.26

T;D

Sift4G

Benign

0.11

T;T

Polyphen

0.0080

B;.

Vest4

0.16

MPC

0.49

ClinPred

0.013

GERP RS

4.7

Varity_R

0.063

gMVP

0.50

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over