17-49502059-C-T

Variant names:

• chr17-49502059-C-T
• rs9895558
• NM_002507.4:c.67-4C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002507.4(NGFR):​c.67-4C>T variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.00001529
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.316
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -16 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 VariationId is 736086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 275 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002507.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	NM_002507.4	MANE Select	c.67-4C>T		splice_region intron	N/A	NP_002498.1	P08138-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	ENST00000172229.8	TSL:1 MANE Select	c.67-4C>T		splice_region intron	N/A	ENSP00000172229.3	P08138-1
	NGFR	ENST00000504201.1	TSL:2	c.-216-4C>T		splice_region intron	N/A	ENSP00000421731.1	P08138-2
	NGFR	ENST00000509200.5	TSL:4	c.-216-4C>T		splice_region intron	N/A	ENSP00000421514.1

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 272 AN: 142638 Hom.: 1 Cov.: 30

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

GnomAD2 exomes AF: 0.000492 AC: 120 AN: 244004 AF XY: 0.000455

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 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.: 2 Cov.: 35 AF XY: 0.000233 AC XY: 137 AN XY: 587242

African (AFR) AF: 0.00891 AC: 238 AN: 26726

American (AMR) AF: 0.000751 AC: 28 AN: 37278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17126

East Asian (EAS) AF: 0.00 AC: 0 AN: 21594

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4408

European-Non Finnish (NFE) AF: 0.00000320 AC: 3 AN: 936968

Other (OTH) AF: 0.000573 AC: 25 AN: 43608

GnomAD4 genome AF: 0.00193 AC: 275 AN: 142756 Hom.: 2 Cov.: 30 AF XY: 0.00188 AC XY: 130 AN XY: 69102

African (AFR) AF: 0.00666 AC: 263 AN: 39502

American (AMR) AF: 0.000801 AC: 11 AN: 13732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3364

East Asian (EAS) AF: 0.00 AC: 0 AN: 4320

South Asian (SAS) AF: 0.00 AC: 0 AN: 4154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65406

Other (OTH) AF: 0.000497 AC: 1 AN: 2014

Alfa AF: 0.000906 Hom.: 0

Bravo AF: 0.00223

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.4
DANN	Benign	0.67
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs9895558; hg19: chr17-47579421;