chr17-49510638-C-T

Variant names:

• chr17-49510638-C-T
• rs11466155
• NM_002507.4:c.795C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.553
• Publications: 20 publications found

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)

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.795C>T	p.Gly265Gly	synonymous_variant	Exon 4 of 6	ENST00000172229.8	NP_002498.1
NGFR-AS1	NR_103773.1	n.377+345G>A		intron_variant	Intron 2 of 2
MIR6165	NR_106751.1	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	Appris	UniProt
NGFR	ENST00000172229.8	c.795C>T	p.Gly265Gly	synonymous_variant	Exon 4 of 6	1	NM_002507.4	ENSP00000172229.3
NGFR	ENST00000504201.1	c.513C>T	p.Gly171Gly	synonymous_variant	Exon 4 of 6	2		ENSP00000421731.1
NGFR-AS1	ENST00000514506.1	n.377+345G>A		intron_variant	Intron 2 of 2	2
MIR6165	ENST00000614803.1	n.-179C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38900 AN: 151688 Hom.: 6187 Cov.: 30

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

GnomAD2 exomes AF: 0.307 AC: 76854 AN: 250378 AF XY: 0.317

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 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.: 45 AF XY: 0.330 AC XY: 239930 AN XY: 727148

African (AFR) AF: 0.0671 AC: 2247 AN: 33478

American (AMR) AF: 0.320 AC: 14293 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 5969 AN: 26134

East Asian (EAS) AF: 0.0716 AC: 2841 AN: 39698

South Asian (SAS) AF: 0.449 AC: 38743 AN: 86254

European-Finnish (FIN) AF: 0.374 AC: 19961 AN: 53372

Middle Eastern (MID) AF: 0.228 AC: 1314 AN: 5768

European-Non Finnish (NFE) AF: 0.336 AC: 373201 AN: 1111882

Other (OTH) AF: 0.298 AC: 18003 AN: 60388

GnomAD4 genome AF: 0.256 AC: 38917 AN: 151806 Hom.: 6193 Cov.: 30 AF XY: 0.261 AC XY: 19371 AN XY: 74144

African (AFR) AF: 0.0791 AC: 3279 AN: 41438

American (AMR) AF: 0.288 AC: 4401 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 792 AN: 3464

East Asian (EAS) AF: 0.0887 AC: 456 AN: 5140

South Asian (SAS) AF: 0.459 AC: 2201 AN: 4794

European-Finnish (FIN) AF: 0.362 AC: 3813 AN: 10520

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.337 AC: 22863 AN: 67882

Other (OTH) AF: 0.257 AC: 541 AN: 2104

Alfa AF: 0.304 Hom.: 11497

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
PhyloP100		-0.55
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11466155; hg19: chr17-47588000; COSMIC: COSV50803004; COSMIC: COSV50803004;