7-108422794-T-C

Variant names:

• chr7-108422794-T-C
• rs2300045
• NM_001037132.4:c.-331-23201A>G

Variant summary

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

The NM_001037132.4(NRCAM):​c.-331-23201A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,950 control chromosomes in the GnomAD database, including 18,485 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 0.49 (18485 hom., cov: 32)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 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.-331-23201A>G		intron	N/A	NP_001032209.1	Q92823-1
	NRCAM	NM_001371156.1		c.-331-23201A>G		intron	N/A	NP_001358085.1
	NRCAM	NM_001371131.1		c.-412-23201A>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.-331-23201A>G		intron	N/A	ENSP00000368314.3	Q92823-1
	NRCAM	ENST00000379024.8	TSL:1	c.-331-23201A>G		intron	N/A	ENSP00000368310.4	Q92823-6
	NRCAM	ENST00000351718.8	TSL:1	c.-331-23201A>G		intron	N/A	ENSP00000325269.6	Q92823-4

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74671 AN: 151830 Hom.: 18464 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.337

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.492 AC: 74734 AN: 151950 Hom.: 18485 Cov.: 32 AF XY: 0.490 AC XY: 36395 AN XY: 74286

African (AFR) AF: 0.523 AC: 21648 AN: 41420

American (AMR) AF: 0.458 AC: 6991 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1464 AN: 3468

East Asian (EAS) AF: 0.396 AC: 2043 AN: 5154

South Asian (SAS) AF: 0.479 AC: 2307 AN: 4816

European-Finnish (FIN) AF: 0.504 AC: 5325 AN: 10558

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.493 AC: 33521 AN: 67942

Other (OTH) AF: 0.442 AC: 933 AN: 2112

Alfa AF: 0.484 Hom.: 30157

Bravo AF: 0.486

Asia WGS AF: 0.386 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.83
DANN	Benign	0.44
PhyloP100		-0.88
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: rs2300045; hg19: chr7-108063238;