rs2300043

Variant names:

• chr7-108422651-G-C
• rs2300043
• NM_001037132.4:c.-331-23058C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-108422651-G-C
• chr7-108422651-G-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.-331-23058C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,774 control chromosomes in the GnomAD database, including 9,161 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 0.34 (9161 hom., cov: 32)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 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.-331-23058C>G		intron	N/A	NP_001032209.1	Q92823-1
	NRCAM	NM_001371156.1		c.-331-23058C>G		intron	N/A	NP_001358085.1
	NRCAM	NM_001371131.1		c.-412-23058C>G		intron	N/A	NP_001358060.1	Q92823-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRCAM	ENST00000379028.8	TSL:5 MANE Select	c.-331-23058C>G		intron	N/A	ENSP00000368314.3	Q92823-1
	NRCAM	ENST00000379024.8	TSL:1	c.-331-23058C>G		intron	N/A	ENSP00000368310.4	Q92823-6
	NRCAM	ENST00000351718.8	TSL:1	c.-331-23058C>G		intron	N/A	ENSP00000325269.6	Q92823-4

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51046 AN: 151656 Hom.: 9157 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.371

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.336 AC: 51061 AN: 151774 Hom.: 9161 Cov.: 32 AF XY: 0.341 AC XY: 25331 AN XY: 74224

African (AFR) AF: 0.195 AC: 8047 AN: 41362

American (AMR) AF: 0.408 AC: 6224 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1559 AN: 3468

East Asian (EAS) AF: 0.504 AC: 2595 AN: 5150

South Asian (SAS) AF: 0.446 AC: 2143 AN: 4806

European-Finnish (FIN) AF: 0.371 AC: 3917 AN: 10550

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25361 AN: 67874

Other (OTH) AF: 0.380 AC: 801 AN: 2110

Alfa AF: 0.353 Hom.: 1242

Bravo AF: 0.334

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.73
PhyloP100		0.036
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: rs2300043; hg19: chr7-108063095; COSMIC: COSV107418460;