rs439587

Variant names:

• chr7-108148806-A-C
• rs439587
• NM_001037132.4:c.*1104T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-108148806-A-C
• chr7-108148806-A-G
• chr7-108148806-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037132.4(NRCAM):​c.*1104T>G variant causes a 3 prime UTR 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 NM_001037132.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 7 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037132.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRCAM	NM_001037132.4	MANE Select	c.*1104T>G		3_prime_UTR	Exon 33 of 33	NP_001032209.1
	NRCAM	NM_001371156.1		c.*1104T>G		3_prime_UTR	Exon 33 of 33	NP_001358085.1
	NRCAM	NM_001371131.1		c.*1104T>G		3_prime_UTR	Exon 34 of 34	NP_001358060.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRCAM	ENST00000379028.8	TSL:5 MANE Select	c.*1104T>G		3_prime_UTR	Exon 33 of 33	ENSP00000368314.3
	NRCAM	ENST00000379024.8	TSL:1	c.*1104T>G		3_prime_UTR	Exon 30 of 30	ENSP00000368310.4
	NRCAM	ENST00000351718.8	TSL:1	c.*1104T>G		3_prime_UTR	Exon 28 of 28	ENSP00000325269.6

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115960 AN: 151966 Hom.: 45426 Cov.: 33

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.: 78 Cov.: 0 AF XY: 0.750 AC XY: 126 AN XY: 168

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.745 AC: 204 AN: 274

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.763 AC: 116021 AN: 152084 Hom.: 45433 Cov.: 33 AF XY: 0.759 AC XY: 56454 AN XY: 74338

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.8
DANN	Benign	0.81
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs439587; hg19: chr7-107789251;