Genetic Variant NM_002507.4:c.795C>T (chr17-49510638-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_002507.4(NGFR):c.795C>T(p.Gly265Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,613,500 control chromosomes in the GnomAD database, including 87,523 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 0.26 ( 6193 hom., cov: 30)

Exomes 𝑓: 0.33 ( 81330 hom. )

Consequence

NGFR
NM_002507.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.553

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:

MIR6165 (HGNC:50197): (microRNA 6165) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6165 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP7

Synonymous conserved (PhyloP=-0.553 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NGFR	NM_002507.4 link	c.795C>T	p.Gly265Gly	synonymous_variant	Exon 4 of 6	ENST00000172229.8	NP_002498.1	P08138-1
NGFR-AS1	NR_103773.1 link	n.377+345G>A		intron_variant	Intron 2 of 2
MIR6165	NR_106751.1 link	n.-179C>T		upstream_gene_variant
MIR6165	unassigned_transcript_3060	n.-187C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NGFR	ENST00000172229.8 link	c.795C>T	p.Gly265Gly	synonymous_variant	Exon 4 of 6	1	NM_002507.4	ENSP00000172229.3	P08138-1
NGFR	ENST00000504201.1 link	c.513C>T	p.Gly171Gly	synonymous_variant	Exon 4 of 6	2		ENSP00000421731.1	P08138-2
NGFR-AS1	ENST00000514506.1 link	n.377+345G>A		intron_variant	Intron 2 of 2	2
MIR6165	ENST00000614803.1 link	n.-179C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38900

AN:

151688

Hom.:

6187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0793

Gnomad AMI

AF:

0.557

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.0883

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.232

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.254

GnomAD3 exomes

AF:

0.307

AC:

76854

AN:

250378

Hom.:

13083

AF XY:

0.317

AC XY:

42937

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.0761

Gnomad AMR exome

AF:

0.323

Gnomad ASJ exome

AF:

0.222

Gnomad EAS exome

AF:

0.0877

Gnomad SAS exome

AF:

0.449

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.328

Gnomad OTH exome

AF:

0.298

GnomAD4 exome

AF:

0.326

AC:

476572

AN:

1461694

Hom.:

81330

Cov.:

AF XY:

0.330

AC XY:

239930

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.0671

Gnomad4 AMR exome

AF:

0.320

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.0716

Gnomad4 SAS exome

AF:

0.449

Gnomad4 FIN exome

AF:

0.374

Gnomad4 NFE exome

AF:

0.336

Gnomad4 OTH exome

AF:

0.298

GnomAD4 genome

AF:

0.256

AC:

38917

AN:

151806

Hom.:

6193

Cov.:

AF XY:

0.261

AC XY:

19371

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.0791

Gnomad4 AMR

AF:

0.288

Gnomad4 ASJ

AF:

0.229

Gnomad4 EAS

AF:

0.0887

Gnomad4 SAS

AF:

0.459

Gnomad4 FIN

AF:

0.362

Gnomad4 NFE

AF:

0.337

Gnomad4 OTH

AF:

0.257

Alfa

AF:

0.299

Hom.:

6104

Bravo

AF:

0.236

Asia WGS

AF:

0.287

AC:

997

AN:

3478

EpiCase

AF:

0.323

EpiControl

AF:

0.320

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.8

DANN

Benign

0.85

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