Variant 17-49502059-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002507.4(NGFR):c.67-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000425 in 1,340,598 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 30)

Exomes 𝑓: 0.00025 ( 2 hom. )

Consequence

NGFR
NM_002507.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001529

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.316

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

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

BP6

Variant 17-49502059-C-T is Benign according to our data. Variant chr17-49502059-C-T is described in ClinVar as [Benign]. Clinvar id is 736086.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 272 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NGFR	NM_002507.4 linkuse as main transcript	c.67-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000172229.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
NGFR	ENST00000172229.8 linkuse as main transcript	c.67-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_002507.4	P1	P08138-1
NGFR	ENST00000504201.1 linkuse as main transcript	c.-216-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2			P08138-2
NGFR	ENST00000509200.5 linkuse as main transcript	c.-216-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	4

Frequencies

GnomAD3 genomes

AF:

0.00191

AC:

272

AN:

142638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00660

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000802

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000502

GnomAD3 exomes

AF:

0.000492

AC:

120

AN:

244004

Hom.:

AF XY:

0.000455

AC XY:

AN XY:

131932

show subpopulations

Gnomad AFR exome

AF:

0.00624

Gnomad AMR exome

AF:

0.000572

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000902

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000246

AC:

295

AN:

1197842

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

137

AN XY:

587242

show subpopulations

Gnomad4 AFR exome

AF:

0.00891

Gnomad4 AMR exome

AF:

0.000751

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000131

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000320

Gnomad4 OTH exome

AF:

0.000573

GnomAD4 genome

AF:

0.00193

AC:

275

AN:

142756

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

130

AN XY:

69102

show subpopulations

Gnomad4 AFR

AF:

0.00666

Gnomad4 AMR

AF:

0.000801

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000497

Alfa

AF:

0.000847

Hom.:

Bravo

AF:

0.00223

Asia WGS

AF:

0.000289

AC:

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 submitter

clinical testing

Invitae

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

Cadd

Benign

9.4

Dann

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000015

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over