Variant 1-235977874-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002508.3(NID1):c.3737A>G(p.Gln1246Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,613,488 control chromosomes in the GnomAD database, including 41,198 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.25 ( 5513 hom., cov: 32)

Exomes 𝑓: 0.20 ( 35685 hom. )

Consequence

NID1
NM_002508.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.151

Variant links:

Genes affected

NID1 (HGNC:7821): (nidogen 1) This gene encodes a member of the nidogen family of basement membrane glycoproteins. The protein interacts with several other components of basement membranes, and may play a role in cell interactions with the extracellular matrix. [provided by RefSeq, Jul 2008]

NID1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.9975407E-5).

BP6

Variant 1-235977874-T-C is Benign according to our data. Variant chr1-235977874-T-C is described in ClinVar as [Benign]. Clinvar id is 1251054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NID1	NM_002508.3 linkuse as main transcript	c.3737A>G	p.Gln1246Arg	missense_variant	20/20	ENST00000264187.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NID1	ENST00000264187.7 linkuse as main transcript	c.3737A>G	p.Gln1246Arg	missense_variant	20/20	1	NM_002508.3	P1	P14543-1
NID1	ENST00000366595.7 linkuse as main transcript	c.3338A>G	p.Gln1113Arg	missense_variant	17/17	1			P14543-2

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37328

AN:

152018

Hom.:

5508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.0802

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.250

GnomAD3 exomes

AF:

0.236

AC:

59156

AN:

250908

Hom.:

8786

AF XY:

0.230

AC XY:

31201

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.356

Gnomad AMR exome

AF:

0.245

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.603

Gnomad SAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.219

GnomAD4 exome

AF:

0.204

AC:

298749

AN:

1461352

Hom.:

35685

Cov.:

AF XY:

0.205

AC XY:

149052

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.355

Gnomad4 AMR exome

AF:

0.243

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.632

Gnomad4 SAS exome

AF:

0.251

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.232

GnomAD4 genome

AF:

0.246

AC:

37355

AN:

152136

Hom.:

5513

Cov.:

AF XY:

0.245

AC XY:

18252

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.352

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.621

Gnomad4 SAS

AF:

0.275

Gnomad4 FIN

AF:

0.150

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.251

Alfa

AF:

0.197

Hom.:

8552

Bravo

AF:

0.258

TwinsUK

AF:

0.171

AC:

633

ALSPAC

AF:

0.177

AC:

684

ESP6500AA

AF:

0.349

AC:

1539

ESP6500EA

AF:

0.175

AC:

1504

ExAC

AF:

0.237

AC:

28784

Asia WGS

AF:

0.397

AC:

1381

AN:

3478

EpiCase

AF:

0.184

EpiControl

AF:

0.184

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.94

DANN

Benign

0.64

DEOGEN2

Benign

0.040

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.42

T;T

MetaRNN

Benign

0.000020

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.7

.;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

1.3

N;N

REVEL

Benign

0.20

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.019

MPC

0.23

ClinPred

0.00098

GERP RS

2.8

Varity_R

0.035

gMVP

0.40

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over