19-49061255-T-C

Variant names:

• chr19-49061255-T-C
• rs115969617
• NM_006179.5:c.*110A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006179.5(NTF4):​c.*110A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,543,994 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (106 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (89 hom.)
• Consequence: NTF4 NM_006179.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.565
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 19-49061255-T-C is Benign according to our data. Variant chr19-49061255-T-C is described in ClinVar as Benign. ClinVar VariationId is 1254939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

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.*110A>G		3_prime_UTR	Exon 2 of 2	NP_006170.1	P34130
	NTF4	NM_001395489.1		c.*110A>G		3_prime_UTR	Exon 3 of 3	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.*110A>G		3_prime_UTR	Exon 2 of 2	ENSP00000469455.1	P34130
	ENSG00000283663	ENST00000599795.5	TSL:2	n.243+500A>G		intron	N/A	ENSP00000470689.1	M0QZQ0
	NTF4	ENST00000594938.2	TSL:5	c.*110A>G		3_prime_UTR	Exon 3 of 3	ENSP00000512387.1	P34130

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 3065 AN: 152072 Hom.: 106 Cov.: 32

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00878

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.00226 AC: 3143 AN: 1391804 Hom.: 89 Cov.: 31 AF XY: 0.00207 AC XY: 1424 AN XY: 687114

African (AFR) AF: 0.0710 AC: 2271 AN: 32002

American (AMR) AF: 0.00521 AC: 195 AN: 37446

Ashkenazi Jewish (ASJ) AF: 0.0000396 AC: 1 AN: 25258

East Asian (EAS) AF: 0.0000272 AC: 1 AN: 36702

South Asian (SAS) AF: 0.00379 AC: 305 AN: 80378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37612

Middle Eastern (MID) AF: 0.00271 AC: 11 AN: 4052

European-Non Finnish (NFE) AF: 0.0000648 AC: 70 AN: 1080336

Other (OTH) AF: 0.00498 AC: 289 AN: 58018

GnomAD4 genome AF: 0.0202 AC: 3070 AN: 152190 Hom.: 106 Cov.: 32 AF XY: 0.0201 AC XY: 1493 AN XY: 74420

African (AFR) AF: 0.0693 AC: 2875 AN: 41514

American (AMR) AF: 0.00877 AC: 134 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00415 AC: 20 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67998

Other (OTH) AF: 0.0123 AC: 26 AN: 2114

Alfa AF: 0.0104 Hom.: 15

Bravo AF: 0.0226

Asia WGS AF: 0.00895 AC: 31 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	-0.93
CADD	Benign	5.2
DANN	Benign	0.53
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs115969617; hg19: chr19-49564512;