dbSNP rs11544636: NRSN1:p.His104Tyr (chr6-24145668-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRSN1	NM_080723.5 link	c.310C>T	p.His104Tyr	missense_variant	Exon 4 of 4	ENST00000378491.9	NP_542454.3	Q8IZ57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NRSN1	ENST00000378491.9 link	c.310C>T	p.His104Tyr	missense_variant	Exon 4 of 4	1	NM_080723.5	ENSP00000367752.4	Q8IZ57
NRSN1	ENST00000378478.5 link	c.310C>T	p.His104Tyr	missense_variant	Exon 4 of 4	1		ENSP00000367739.2	Q8IZ57
NRSN1	ENST00000378477.2 link	c.310C>T	p.His104Tyr	missense_variant	Exon 4 of 4	1		ENSP00000367738.2	Q5VTS0
NRSN1	ENST00000468195.2 link	n.257-9103C>T		intron_variant	Intron 2 of 2	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

GnomAD2 exomes

AF:

0.0189

AC:

4750

AN:

251416

AF XY:

0.0203

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 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

African (AFR)

AF:

0.00344

AC:

115

AN:

33478

American (AMR)

AF:

0.0137

AC:

612

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0286

AC:

748

AN:

26134

East Asian (EAS)

AF:

0.000680

AC:

AN:

39700

South Asian (SAS)

AF:

0.0331

AC:

2859

AN:

86250

European-Finnish (FIN)

AF:

0.0107

AC:

571

AN:

53420

Middle Eastern (MID)

AF:

0.0238

AC:

137

AN:

5766

European-Non Finnish (NFE)

AF:

0.0241

AC:

26817

AN:

1111960

Other (OTH)

AF:

0.0199

AC:

1201

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

1693

3386

5079

6772

8465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0165

AC:

2515

AN:

152292

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1201

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00356

AC:

148

AN:

41570

American (AMR)

AF:

0.0156

AC:

238

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

AN:

3472

East Asian (EAS)

AF:

0.00193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0338

AC:

163

AN:

4820

European-Finnish (FIN)

AF:

0.0113

AC:

120

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0237

AC:

1609

AN:

68020

Other (OTH)

AF:

0.0147

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

129

258

388

517

646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0211

Hom.:

110

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

(source)

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;.

PhyloP100

6.1

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

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs11544636

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over