Variant rs11544636 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_080723.5(NRSN1):c.310C>T(p.His104Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0221 in 1,614,114 control chromosomes in the GnomAD database, including 493 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.017 ( 39 hom., cov: 32)

Exomes 𝑓: 0.023 ( 454 hom. )

Consequence

NRSN1
NM_080723.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.13

Variant links:

Genes affected

NRSN1 (HGNC:17881): (neurensin 1) Predicted to be involved in nervous system development. Predicted to be located in cytoplasmic vesicle and growth cone. Predicted to be active in neuron projection; neuronal cell body; and transport vesicle. [provided by Alliance of Genome Resources, Apr 2022]

NRSN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037810206).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0165 (2515/152292) while in subpopulation SAS AF= 0.0338 (163/4820). AF 95% confidence interval is 0.0296. There are 39 homozygotes in gnomad4. There are 1201 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRSN1	NM_080723.5 linkuse as main transcript	c.310C>T	p.His104Tyr	missense_variant	4/4	ENST00000378491.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NRSN1	ENST00000378491.9 linkuse as main transcript	c.310C>T	p.His104Tyr	missense_variant	4/4	1	NM_080723.5	P1
NRSN1	ENST00000378478.5 linkuse as main transcript	c.310C>T	p.His104Tyr	missense_variant	4/4	1		P1
NRSN1	ENST00000378477.2 linkuse as main transcript	c.310C>T	p.His104Tyr	missense_variant	4/4	1
NRSN1	ENST00000468195.2 linkuse as main transcript	n.257-9103C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2515

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00357

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.0340

Gnomad FIN

AF:

0.0113

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0236

Gnomad OTH

AF:

0.0149

GnomAD3 exomes

AF:

0.0189

AC:

4750

AN:

251416

Hom.:

AF XY:

0.0203

AC XY:

2763

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00351

Gnomad AMR exome

AF:

0.0133

Gnomad ASJ exome

AF:

0.0259

Gnomad EAS exome

AF:

0.000870

Gnomad SAS exome

AF:

0.0318

Gnomad FIN exome

AF:

0.00919

Gnomad NFE exome

AF:

0.0233

Gnomad OTH exome

AF:

0.0215

GnomAD4 exome

AF:

0.0226

AC:

33087

AN:

1461822

Hom.:

454

Cov.:

AF XY:

0.0233

AC XY:

16960

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00344

Gnomad4 AMR exome

AF:

0.0137

Gnomad4 ASJ exome

AF:

0.0286

Gnomad4 EAS exome

AF:

0.000680

Gnomad4 SAS exome

AF:

0.0331

Gnomad4 FIN exome

AF:

0.0107

Gnomad4 NFE exome

AF:

0.0241

Gnomad4 OTH exome

AF:

0.0199

GnomAD4 genome

AF:

0.0165

AC:

2515

AN:

152292

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1201

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00356

Gnomad4 AMR

AF:

0.0156

Gnomad4 ASJ

AF:

0.0268

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0338

Gnomad4 FIN

AF:

0.0113

Gnomad4 NFE

AF:

0.0237

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0219

Hom.:

Bravo

AF:

0.0159

TwinsUK

AF:

0.0227

AC:

ALSPAC

AF:

0.0280

AC:

108

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.0243

AC:

209

ExAC

AF:

0.0191

AC:

2314

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0242

EpiControl

AF:

0.0264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.049

T;T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.090

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

.;T;T

MetaRNN

Benign

0.0038

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.

MutationTaster

Benign

0.88

D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.6

N;.;N

REVEL

Benign

0.097

Sift

Benign

0.039

D;.;D

Sift4G

Benign

0.074

T;T;T

Polyphen

0.26

B;B;.

Vest4

0.074

MPC

0.34

ClinPred

0.029

GERP RS

5.4

Varity_R

0.14

gMVP

0.61

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over