Variant 1-235977934-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002508.3(NID1):c.3677C>T(p.Thr1226Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000991 in 1,614,172 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0047 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 11 hom. )

Consequence

NID1
NM_002508.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.38

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=0.009787917).

BP6

Variant 1-235977934-G-A is Benign according to our data. Variant chr1-235977934-G-A is described in ClinVar as [Benign]. Clinvar id is 789961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-235977934-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00468 (713/152338) while in subpopulation AFR AF= 0.0164 (683/41562). AF 95% confidence interval is 0.0154. There are 8 homozygotes in gnomad4. There are 355 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NID1	NM_002508.3 link	c.3677C>T	p.Thr1226Ile	missense_variant	20/20	ENST00000264187.7	NP_002499.2	P14543-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NID1	ENST00000264187.7 link	c.3677C>T	p.Thr1226Ile	missense_variant	20/20	1	NM_002508.3	ENSP00000264187.6		P14543-1
NID1	ENST00000366595.7 link	c.3278C>T	p.Thr1093Ile	missense_variant	17/17	1		ENSP00000355554.3		P14543-2

Frequencies

GnomAD3 genomes

AF:

0.00466

AC:

710

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00128

AC:

321

AN:

251224

Hom.:

AF XY:

0.000943

AC XY:

128

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.0165

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000607

AC:

887

AN:

1461834

Hom.:

Cov.:

AF XY:

0.000606

AC XY:

441

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0176

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000113

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00468

AC:

713

AN:

152338

Hom.:

Cov.:

AF XY:

0.00477

AC XY:

355

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0164

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00206

Hom.:

Bravo

AF:

0.00500

ESP6500AA

AF:

0.0166

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00171

AC:

208

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

.;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0098

T;T

MetaSVM

Uncertain

0.74

MutationAssessor

Uncertain

2.3

.;M

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-2.1

N;N

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

1.0

D;D

Vest4

0.40

MVP

0.94

MPC

0.25

ClinPred

0.027

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

gMVP

0.73

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