19-49062161-G-A

Variant names:

• chr19-49062161-G-A
• rs77113200
• NM_006179.5:c.-12-152C>T

Variant summary

Our verdict is Benign. The variant received -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]

ENSG00000283663 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1568 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTF4	NM_006179.5	c.-12-152C>T		intron_variant	Intron 1 of 1	ENST00000593537.2	NP_006170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTF4	ENST00000593537.2	c.-12-152C>T		intron_variant	Intron 1 of 1	6	NM_006179.5	ENSP00000469455.1
ENSG00000283663	ENST00000599795.5	n.-12-152C>T		intron_variant	Intron 2 of 6	2		ENSP00000470689.1

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

African (AFR) AF: 0.00291 AC: 121 AN: 41546

American (AMR) AF: 0.00804 AC: 123 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.0160 AC: 170 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0166 AC: 1131 AN: 68026

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

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

May 10, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.44
PhyloP100		-0.27
PromoterAI		-0.026	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Publications

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Other links and lift over

dbSNP: rs77113200; hg19: chr19-49565418;