rs147759837

Variant names:

• chr19-49062073-G-A
• rs147759837
• NM_006179.5:c.-12-64C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006179.5(NTF4):​c.-12-64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,420,412 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (11 hom.)
• Consequence: NTF4 NM_006179.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.678
• Publications: 0 publications found

Genes affected

NTF4 (HGNC:8024): (neurotrophin 4) This gene is a member of a family of neurotrophic factors, neurotrophins, that control survival and differentiation of mammalian neurons. The expression of this gene is ubiquitous and less influenced by environmental signals. While knock-outs of other neurotrophins including nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 prove lethal during early postnatal development, NTF5-deficient mice only show minor cellular deficits and develop normally to adulthood. [provided by RefSeq, Jul 2008]

NTF4 Gene-Disease associations (from GenCC):

• glaucoma 1, open angle, O

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000283663 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 19-49062073-G-A is Benign according to our data. Variant chr19-49062073-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1344980.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00654 (997/152346) while in subpopulation AFR AF = 0.0229 (952/41566). AF 95% confidence interval is 0.0217. There are 9 homozygotes in GnomAd4. There are 472 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 997 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006179.5. 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
	NTF4	NM_006179.5	MANE Select	c.-12-64C>T		intron	N/A	NP_006170.1	P34130
	NTF4	NM_001395489.1		c.-12-64C>T		intron	N/A	NP_001382418.1	P34130

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTF4	ENST00000593537.2	TSL:6 MANE Select	c.-12-64C>T		intron	N/A	ENSP00000469455.1	P34130
	ENSG00000283663	ENST00000599795.5	TSL:2	n.-12-64C>T		intron	N/A	ENSP00000470689.1	M0QZQ0
	NTF4	ENST00000594938.2	TSL:5	c.-12-64C>T		intron	N/A	ENSP00000512387.1	P34130

Frequencies

GnomAD3 genomes AF: 0.00652 AC: 992 AN: 152228 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

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: 0.000103

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.000592 AC: 751 AN: 1268066 Hom.: 11 AF XY: 0.000466 AC XY: 285 AN XY: 611490

African (AFR) AF: 0.0237 AC: 663 AN: 28028

American (AMR) AF: 0.000779 AC: 15 AN: 19246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18668

East Asian (EAS) AF: 0.00 AC: 0 AN: 34416

South Asian (SAS) AF: 0.0000517 AC: 3 AN: 57990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32004

Middle Eastern (MID) AF: 0.000266 AC: 1 AN: 3756

European-Non Finnish (NFE) AF: 0.00000979 AC: 10 AN: 1021162

Other (OTH) AF: 0.00112 AC: 59 AN: 52796

GnomAD4 genome AF: 0.00654 AC: 997 AN: 152346 Hom.: 9 Cov.: 32 AF XY: 0.00634 AC XY: 472 AN XY: 74502

African (AFR) AF: 0.0229 AC: 952 AN: 41566

American (AMR) AF: 0.00183 AC: 28 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68034

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00789 Hom.: 1

Bravo AF: 0.00726

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.0
DANN	Benign	0.85
PhyloP100		0.68
PromoterAI		0.0036	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs147759837; hg19: chr19-49565330;