19-49061255-T-C

Position:

• chr19-49061255-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000283663 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTF4	NM_006179.5	c.*110A>G		3_prime_UTR_variant	2/2	ENST00000593537.2	NP_006170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTF4	ENST00000593537.2	c.*110A>G		3_prime_UTR_variant	2/2	6	NM_006179.5	ENSP00000469455.1
ENSG00000283663	ENST00000599795.5	n.243+500A>G		intron_variant		2		ENSP00000470689.1

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

Gnomad4 AFR exome AF: 0.0710

Gnomad4 AMR exome AF: 0.00521

Gnomad4 ASJ exome AF: 0.0000396

Gnomad4 EAS exome AF: 0.0000272

Gnomad4 SAS exome AF: 0.00379

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000648

Gnomad4 OTH exome AF: 0.00498

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

Gnomad4 AFR AF: 0.0693

Gnomad4 AMR AF: 0.00877

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00931 Hom.: 13

Bravo AF: 0.0226

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.2
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs115969617; hg19: chr19-49564512;