Genetic Variant NGFR:c.569-62G>T (chr17-49510350-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002507.4(NGFR):c.569-62G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,593,668 control chromosomes in the GnomAD database, including 7,234 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.076 ( 558 hom., cov: 32)

Exomes 𝑓: 0.094 ( 6676 hom. )

Consequence

NGFR
NM_002507.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.117

Publications

13 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGFR	NM_002507.4 link	c.569-62G>T		intron_variant	Intron 3 of 5	ENST00000172229.8	NP_002498.1	P08138-1
NGFR-AS1	NR_103773.1 link	n.377+633C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NGFR	ENST00000172229.8 link	c.569-62G>T	intron_variant	Intron 3 of 5	1	NM_002507.4	ENSP00000172229.3	P08138-1
NGFR	ENST00000504201.1 link	c.287-62G>T	intron_variant	Intron 3 of 5	2		ENSP00000421731.1	P08138-2
NGFR-AS1	ENST00000514506.1 link	n.377+633C>A	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0765

AC:

11633

AN:

152044

Hom.:

557

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0290

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.0856

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.0871

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0720

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0951

Gnomad OTH

AF:

0.0839

GnomAD4 exome

AF:

0.0936

AC:

134914

AN:

1441506

Hom.:

6676

AF XY:

0.0951

AC XY:

67883

AN XY:

714170

show subpopulations

African (AFR)

AF:

0.0286

AC:

948

AN:

33128

American (AMR)

AF:

0.0883

AC:

3892

AN:

44078

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

3797

AN:

25234

East Asian (EAS)

AF:

0.0889

AC:

3501

AN:

39366

South Asian (SAS)

AF:

0.136

AC:

11555

AN:

84808

European-Finnish (FIN)

AF:

0.0685

AC:

3414

AN:

49852

Middle Eastern (MID)

AF:

0.105

AC:

595

AN:

5682

European-Non Finnish (NFE)

AF:

0.0923

AC:

101476

AN:

1099834

Other (OTH)

AF:

0.0964

AC:

5736

AN:

59524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

6653

13306

19960

26613

33266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3822

7644

11466

15288

19110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0765

AC:

11636

AN:

152162

Hom.:

558

Cov.:

AF XY:

0.0767

AC XY:

5708

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0290

AC:

1205

AN:

41508

American (AMR)

AF:

0.0855

AC:

1308

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

583

AN:

3468

East Asian (EAS)

AF:

0.0873

AC:

451

AN:

5168

South Asian (SAS)

AF:

0.131

AC:

631

AN:

4826

European-Finnish (FIN)

AF:

0.0720

AC:

764

AN:

10606

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0951

AC:

6466

AN:

67978

Other (OTH)

AF:

0.0835

AC:

176

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

542

1084

1625

2167

2709

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0908

Hom.:

520

Bravo

AF:

0.0746

Asia WGS

AF:

0.123

AC:

429

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.8

(source)

DANN

Benign

0.66

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over