rs754065091

Variant names:

• chr19-5827731-C-T
• rs754065091
• NM_004558.5:c.170-18C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-5827731-C-T
• chr19-5827731-C-A
• chr19-5827731-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_004558.5(NRTN):​c.170-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00076 in 858,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00084 (0 hom.)
• Consequence: NRTN NM_004558.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.422
• Publications: 0 publications found

Genes affected

NRTN (HGNC:8007): (neurturin) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein signals through the RET receptor tyrosine kinase and a GPI-linked coreceptor, and promotes survival of neuronal populations. A neurturin mutation has been described in a family with Hirschsprung Disease. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 19-5827731-C-T is Benign according to our data. Variant chr19-5827731-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 259426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004558.5. 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
	NRTN	NM_004558.5	MANE Select	c.170-18C>T		intron	N/A	NP_004549.1	Q99748

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRTN	ENST00000303212.3	TSL:1 MANE Select	c.170-18C>T		intron	N/A	ENSP00000302648.1	Q99748
	NRTN	ENST00000879152.1		c.170-18C>T		intron	N/A	ENSP00000549211.1
	NRTN	ENST00000936080.1		c.170-18C>T		intron	N/A	ENSP00000606139.1

Frequencies

GnomAD3 genomes AF: 0.000382 AC: 56 AN: 146472 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000406

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000473

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000226 AC: 12 AN: 53052 AF XY: 0.000330

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000254

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000837 AC: 596 AN: 711758 Hom.: 0 Cov.: 15 AF XY: 0.000824 AC XY: 280 AN XY: 340004

African (AFR) AF: 0.00 AC: 0 AN: 15314

American (AMR) AF: 0.000490 AC: 5 AN: 10212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8000

East Asian (EAS) AF: 0.00 AC: 0 AN: 17050

South Asian (SAS) AF: 0.000763 AC: 12 AN: 15718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9756

Middle Eastern (MID) AF: 0.000296 AC: 1 AN: 3374

European-Non Finnish (NFE) AF: 0.000932 AC: 564 AN: 605460

Other (OTH) AF: 0.000521 AC: 14 AN: 26874

GnomAD4 genome AF: 0.000382 AC: 56 AN: 146472 Hom.: 0 Cov.: 31 AF XY: 0.000350 AC XY: 25 AN XY: 71450

African (AFR) AF: 0.000173 AC: 7 AN: 40360

American (AMR) AF: 0.000406 AC: 6 AN: 14792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.00 AC: 0 AN: 4484

South Asian (SAS) AF: 0.000473 AC: 2 AN: 4230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.000617 AC: 41 AN: 66452

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000408

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.3
DANN	Benign	0.96
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs754065091; hg19: chr19-5827742;