Variant rs7913176 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_198514.4(NHLRC2):c.940G>A(p.Val314Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,608,448 control chromosomes in the GnomAD database, including 63,487 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.25 ( 5162 hom., cov: 32)

Exomes 𝑓: 0.28 ( 58325 hom. )

Consequence

NHLRC2
NM_198514.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.65

Variant links:

Genes affected

NHLRC2 (HGNC:24731): (NHL repeat containing 2) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

NHLRC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014792085).

BP6

Variant 10-113884281-G-A is Benign according to our data. Variant chr10-113884281-G-A is described in ClinVar as [Benign]. Clinvar id is 3059194.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHLRC2	NM_198514.4 linkuse as main transcript	c.940G>A	p.Val314Ile	missense_variant	5/11	ENST00000369301.3	NP_940916.2	Q8NBF2-1Q7Z658
NHLRC2	XM_011539769.4 linkuse as main transcript	c.940G>A	p.Val314Ile	missense_variant	5/11		XP_011538071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHLRC2	ENST00000369301.3 linkuse as main transcript	c.940G>A	p.Val314Ile	missense_variant	5/11	2	NM_198514.4	ENSP00000358307.3		Q8NBF2-1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37925

AN:

151572

Hom.:

5157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.226

GnomAD3 exomes

AF:

0.276

AC:

69339

AN:

250812

Hom.:

9987

AF XY:

0.273

AC XY:

37059

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.217

Gnomad EAS exome

AF:

0.330

Gnomad SAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.291

Gnomad OTH exome

AF:

0.270

GnomAD4 exome

AF:

0.279

AC:

406600

AN:

1456756

Hom.:

58325

Cov.:

AF XY:

0.277

AC XY:

201023

AN XY:

724860

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.266

Gnomad4 ASJ exome

AF:

0.223

Gnomad4 EAS exome

AF:

0.285

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.386

Gnomad4 NFE exome

AF:

0.287

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.250

AC:

37937

AN:

151692

Hom.:

5162

Cov.:

AF XY:

0.253

AC XY:

18745

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.152

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.329

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.392

Gnomad4 NFE

AF:

0.287

Gnomad4 OTH

AF:

0.223

Alfa

AF:

0.273

Hom.:

13934

Bravo

AF:

0.238

TwinsUK

AF:

0.295

AC:

1095

ALSPAC

AF:

0.294

AC:

1134

ESP6500AA

AF:

0.155

AC:

684

ESP6500EA

AF:

0.282

AC:

2422

ExAC

AF:

0.272

AC:

32986

Asia WGS

AF:

0.252

AC:

875

AN:

3478

EpiCase

AF:

0.271

EpiControl

AF:

0.265

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NHLRC2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0015

Eigen

Benign

-0.074

Eigen_PC

Benign

0.073

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

0.25

REVEL

Uncertain

0.30

Sift

Benign

0.43

Sift4G

Benign

0.64

Polyphen

0.55

Vest4

0.047

MPC

0.11

ClinPred

0.014

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.082

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over