rs2216259

Variant names:

• chr7-108375106-A-C
• rs2216259
• NM_001037132.4:c.-174+24330T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-108375106-A-C
• chr7-108375106-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.-174+24330T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,842 control chromosomes in the GnomAD database, including 8,754 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 0.33 (8754 hom., cov: 31)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.-174+24330T>G		intron_variant	Intron 2 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.-174+24330T>G		intron_variant	Intron 2 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49992 AN: 151722 Hom.: 8737 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.330 AC: 50042 AN: 151842 Hom.: 8754 Cov.: 31 AF XY: 0.336 AC XY: 24967 AN XY: 74212

African (AFR) AF: 0.383 AC: 15854 AN: 41414

American (AMR) AF: 0.338 AC: 5152 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3466

East Asian (EAS) AF: 0.598 AC: 3073 AN: 5136

South Asian (SAS) AF: 0.439 AC: 2112 AN: 4810

European-Finnish (FIN) AF: 0.319 AC: 3366 AN: 10562

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18401 AN: 67906

Other (OTH) AF: 0.325 AC: 684 AN: 2106

Alfa AF: 0.335 Hom.: 2031

Bravo AF: 0.335

Asia WGS AF: 0.458 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.11
DANN	Benign	0.46
PhyloP100		-1.6
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: rs2216259; hg19: chr7-108015550;