7-108201288-C-T

Variant names:

• chr7-108201288-C-T
• rs405945
• NM_001037132.4:c.1208-3189G>A

Variant summary

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

The NM_001037132.4(NRCAM):​c.1208-3189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,836 control chromosomes in the GnomAD database, including 13,463 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 0.38 (13463 hom., cov: 31)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 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.1208-3189G>A		intron	N/A	NP_001032209.1	Q92823-1
	NRCAM	NM_001371156.1		c.1208-3189G>A		intron	N/A	NP_001358085.1
	NRCAM	NM_001371131.1		c.1208-3189G>A		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.1208-3189G>A		intron	N/A	ENSP00000368314.3	Q92823-1
	NRCAM	ENST00000379024.8	TSL:1	c.1151-3189G>A		intron	N/A	ENSP00000368310.4	Q92823-6
	NRCAM	ENST00000351718.8	TSL:1	c.1190-3189G>A		intron	N/A	ENSP00000325269.6	Q92823-4

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58116 AN: 151738 Hom.: 13470 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.383 AC: 58112 AN: 151836 Hom.: 13463 Cov.: 31 AF XY: 0.391 AC XY: 28991 AN XY: 74160

African (AFR) AF: 0.131 AC: 5435 AN: 41408

American (AMR) AF: 0.537 AC: 8189 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1812 AN: 3468

East Asian (EAS) AF: 0.808 AC: 4164 AN: 5154

South Asian (SAS) AF: 0.464 AC: 2221 AN: 4786

European-Finnish (FIN) AF: 0.433 AC: 4551 AN: 10510

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.444 AC: 30178 AN: 67958

Other (OTH) AF: 0.403 AC: 849 AN: 2108

Alfa AF: 0.413 Hom.: 2910

Bravo AF: 0.383

Asia WGS AF: 0.565 AC: 1961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.79
DANN	Benign	0.62
PhyloP100		-0.38
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: rs405945; hg19: chr7-107841732;