rs7224806

Positions:

• chr17-49514102-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002507.4(NGFR):​c.*1093T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 152,542 control chromosomes in the GnomAD database, including 893 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 0.10 (890 hom., cov: 32)
  • Exomes 𝑓: 0.11 (3 hom.)
• Consequence: NGFR NM_002507.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGFR	NM_002507.4	c.*1093T>C		3_prime_UTR_variant	6/6	ENST00000172229.8	NP_002498.1
NGFR-AS1	NR_103773.1	n.247-2989A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGFR	ENST00000172229.8	c.*1093T>C		3_prime_UTR_variant	6/6	1	NM_002507.4	ENSP00000172229	P1
NGFR-AS1	ENST00000514506.1	n.247-2989A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15180 AN: 152050 Hom.: 891 Cov.: 32

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0882

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.0663

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.115 AC: 43 AN: 374 Hom.: 3 Cov.: 0 AF XY: 0.102 AC XY: 25 AN XY: 244

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.0997 AC: 15174 AN: 152168 Hom.: 890 Cov.: 32 AF XY: 0.0997 AC XY: 7415 AN XY: 74410

Gnomad4 AFR AF: 0.0989

Gnomad4 AMR AF: 0.0881

Gnomad4 ASJ AF: 0.0697

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.0665

Gnomad4 FIN AF: 0.0959

Gnomad4 NFE AF: 0.0960

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0982 Hom.: 885

Bravo AF: 0.104

Asia WGS AF: 0.134 AC: 465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.2
DANN	Benign	0.76

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

Other links and lift over

dbSNP: rs7224806; hg19: chr17-47591464;