dbSNP rs439587: NRCAM:n.1652T>G (chr7-108148806-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000522550.2(NRCAM):n.1652T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,364 control chromosomes in the GnomAD database, including 45,511 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.76 ( 45433 hom., cov: 33)

Exomes 𝑓: 0.75 ( 78 hom. )

Consequence

NRCAM
ENST00000522550.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with neuromuscular and skeletal abnormalities
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

NRCAM 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 (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4 link	c.*1104T>G		3_prime_UTR_variant	Exon 33 of 33	ENST00000379028.8	NP_001032209.1	Q92823-1Q14CA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8 link	c.*1104T>G		3_prime_UTR_variant	Exon 33 of 33	5	NM_001037132.4	ENSP00000368314.3		Q92823-1

Frequencies

GnomAD3 genomes

AF:

0.763

AC:

115960

AN:

151966

Hom.:

45426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.567

Gnomad AMI

AF:

0.910

Gnomad AMR

AF:

0.821

Gnomad ASJ

AF:

0.890

Gnomad EAS

AF:

0.836

Gnomad SAS

AF:

0.726

Gnomad FIN

AF:

0.762

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.857

Gnomad OTH

AF:

0.774

GnomAD4 exome

AF:

0.750

AC:

210

AN:

280

Hom.:

Cov.:

AF XY:

0.750

AC XY:

126

AN XY:

168

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.745

AC:

204

AN:

274

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.763

AC:

116021

AN:

152084

Hom.:

45433

Cov.:

AF XY:

0.759

AC XY:

56454

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.567

AC:

23491

AN:

41402

American (AMR)

AF:

0.821

AC:

12546

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.890

AC:

3086

AN:

3466

East Asian (EAS)

AF:

0.835

AC:

4323

AN:

5176

South Asian (SAS)

AF:

0.728

AC:

3516

AN:

4828

European-Finnish (FIN)

AF:

0.762

AC:

8077

AN:

10594

Middle Eastern (MID)

AF:

0.793

AC:

233

AN:

294

European-Non Finnish (NFE)

AF:

0.857

AC:

58285

AN:

68012

Other (OTH)

AF:

0.773

AC:

1634

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1328

2656

3985

5313

6641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.826

Hom.:

151030

Bravo

AF:

0.760

Asia WGS

AF:

0.775

AC:

2699

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.8

(source)

DANN

Benign

0.81

PhyloP100

1.3

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over