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GeneBe

17-49506423-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_002507.4(NGFR):c.333C>T(p.Tyr111=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000615 in 1,606,330 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00060 ( 8 hom. )

Consequence

NGFR
NM_002507.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.335
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-AS1 (HGNC:55555): (NGFR antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-49506423-C-T is Benign according to our data. Variant chr17-49506423-C-T is described in ClinVar as [Benign]. Clinvar id is 717409.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.335 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000775 (118/152222) while in subpopulation EAS AF= 0.018 (93/5168). AF 95% confidence interval is 0.015. There are 0 homozygotes in gnomad4. There are 64 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 118 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NGFRNM_002507.4 linkuse as main transcriptc.333C>T p.Tyr111= synonymous_variant 3/6 ENST00000172229.8
NGFR-AS1NR_103773.1 linkuse as main transcriptn.455G>A non_coding_transcript_exon_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NGFRENST00000172229.8 linkuse as main transcriptc.333C>T p.Tyr111= synonymous_variant 3/61 NM_002507.4 P1P08138-1
NGFR-AS1ENST00000514506.1 linkuse as main transcriptn.455G>A non_coding_transcript_exon_variant 3/32
NGFRENST00000504201.1 linkuse as main transcriptc.51C>T p.Tyr17= synonymous_variant 3/62 P08138-2
NGFRENST00000509200.5 linkuse as main transcript downstream_gene_variant 4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000776
AC:
118
AN:
152104
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000507
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0180
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00165
AC:
390
AN:
235888
Hom.:
5
AF XY:
0.00138
AC XY:
179
AN XY:
129958
show subpopulations
Gnomad AFR exome
AF:
0.000410
Gnomad AMR exome
AF:
0.0000879
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0204
Gnomad SAS exome
AF:
0.000462
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00119
GnomAD4 exome
AF:
0.000598
AC:
870
AN:
1454108
Hom.:
8
Cov.:
32
AF XY:
0.000561
AC XY:
406
AN XY:
723548
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.0000673
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0186
Gnomad4 SAS exome
AF:
0.000639
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00105
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000775
AC:
118
AN:
152222
Hom.:
0
Cov.:
31
AF XY:
0.000860
AC XY:
64
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.000506
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0180
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000342
Hom.:
0
Bravo
AF:
0.000888
Asia WGS
AF:
0.0110
AC:
38
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
Cadd
Benign
15
Dann
Benign
0.95

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.

Other links and lift over

dbSNP: rs116693011; hg19: chr17-47583785; COSMIC: COSV99412730; COSMIC: COSV99412730; API