7-108149972-C-T

Position:

chr7-108149972-C-T

Variant summary

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

The NM_001037132.4(NRCAM):c.3853G>A(p.Ala1285Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00137 in 1,613,966 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 17 hom., cov: 33)

Exomes 𝑓: 0.00075 ( 9 hom. )

Consequence

NRCAM
NM_001037132.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.20

Variant links:

Genes affected

NRCAM (HGNC:7994): (neuronal cell adhesion molecule) Cell adhesion molecules (CAMs) are members of the immunoglobulin superfamily. This gene encodes a neuronal cell adhesion molecule with multiple immunoglobulin-like C2-type domains and fibronectin type-III domains. This ankyrin-binding protein is involved in neuron-neuron adhesion and promotes directional signaling during axonal cone growth. This gene is also expressed in non-neural tissues and may play a general role in cell-cell communication via signaling from its intracellular domain to the actin cytoskeleton during directional cell migration. Allelic variants of this gene have been associated with autism and addiction vulnerability. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

NRCAM links:

NRCAM (HGNC:):

NRCAM 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=0.003005296).

BP6

Variant 7-108149972-C-T is Benign according to our data. Variant chr7-108149972-C-T is described in ClinVar as [Benign]. Clinvar id is 714356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00732 (1115/152294) while in subpopulation AFR AF= 0.0254 (1054/41558). AF 95% confidence interval is 0.0241. There are 17 homozygotes in gnomad4. There are 507 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRCAM	NM_001037132.4 linkuse as main transcript	c.3853G>A	p.Ala1285Thr	missense_variant	33/33	ENST00000379028.8	NP_001032209.1	Q92823-1Q14CA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8 linkuse as main transcript	c.3853G>A	p.Ala1285Thr	missense_variant	33/33	5	NM_001037132.4	ENSP00000368314.3		Q92823-1

Frequencies

GnomAD3 genomes

AF:

0.00731

AC:

1112

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00184

AC:

462

AN:

250866

Hom.:

AF XY:

0.00142

AC XY:

193

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.0246

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000745

AC:

1089

AN:

1461672

Hom.:

Cov.:

AF XY:

0.000633

AC XY:

460

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0253

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000710

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00732

AC:

1115

AN:

152294

Hom.:

Cov.:

AF XY:

0.00681

AC XY:

507

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0254

Gnomad4 AMR

AF:

0.00308

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00131

Hom.:

Bravo

AF:

0.00852

ESP6500AA

AF:

0.0261

AC:

115

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00239

AC:

290

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 20, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

NRCAM-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 31, 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

0.075

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.21

T;.;.;.;.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.014

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.86

D;D;D;D;D;.

MetaRNN

Benign

0.0030

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;.;.;.;.;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.71

N;.;N;N;.;N

REVEL

Benign

0.050

Sift

Benign

0.72

T;.;T;T;.;T

Sift4G

Benign

0.85

T;T;T;T;T;T

Polyphen

0.0010

B;.;B;.;.;B

Vest4

0.12

MVP

0.71

MPC

0.23

ClinPred

0.018

GERP RS

5.3

Varity_R

0.030

gMVP

0.21

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