19-49062161-G-A

Position:

• chr19-49062161-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006179.5(NTF4):​c.-12-152C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 152,292 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.010 (9 hom., cov: 32)
• Consequence: NTF4 NM_006179.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.270

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-49062161-G-A is Benign according to our data. Variant chr19-49062161-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1317038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0103 (1568/152292) while in subpopulation NFE AF= 0.0166 (1131/68026). AF 95% confidence interval is 0.0158. There are 9 homozygotes in gnomad4. There are 758 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1568 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTF4	NM_006179.5	c.-12-152C>T		intron_variant		ENST00000593537.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTF4	ENST00000593537.2	c.-12-152C>T		intron_variant			NM_006179.5	P1

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1569 AN: 152174 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00292

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.00574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0103 AC: 1568 AN: 152292 Hom.: 9 Cov.: 32 AF XY: 0.0102 AC XY: 758 AN XY: 74462

Gnomad4 AFR AF: 0.00291

Gnomad4 AMR AF: 0.00804

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0160

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.0136 Hom.: 4

Bravo AF: 0.00966

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77113200; hg19: chr19-49565418;