7-108447879-A-T

Variant names:

• chr7-108447879-A-T
• rs1859767
• NM_001037132.4:c.-332+8364T>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.-332+8364T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,976 control chromosomes in the GnomAD database, including 9,809 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 0.35 (9809 hom., cov: 32)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRCAM	NM_001037132.4	MANE Select	c.-332+8364T>A		intron	N/A	NP_001032209.1
	NRCAM	NM_001371156.1		c.-332+8364T>A		intron	N/A	NP_001358085.1
	NRCAM	NM_001371131.1		c.-413+8364T>A		intron	N/A	NP_001358060.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRCAM	ENST00000379028.8	TSL:5 MANE Select	c.-332+8364T>A		intron	N/A	ENSP00000368314.3
	NRCAM	ENST00000379024.8	TSL:1	c.-332+8364T>A		intron	N/A	ENSP00000368310.4
	NRCAM	ENST00000351718.8	TSL:1	c.-332+8364T>A		intron	N/A	ENSP00000325269.6

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53220 AN: 151858 Hom.: 9788 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.351 AC: 53292 AN: 151976 Hom.: 9809 Cov.: 32 AF XY: 0.355 AC XY: 26368 AN XY: 74258

African (AFR) AF: 0.456 AC: 18862 AN: 41408

American (AMR) AF: 0.338 AC: 5164 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1074 AN: 3468

East Asian (EAS) AF: 0.419 AC: 2164 AN: 5166

South Asian (SAS) AF: 0.380 AC: 1831 AN: 4818

European-Finnish (FIN) AF: 0.358 AC: 3780 AN: 10544

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19433 AN: 67972

Other (OTH) AF: 0.322 AC: 681 AN: 2114

Alfa AF: 0.169 Hom.: 326

Bravo AF: 0.353

Asia WGS AF: 0.365 AC: 1266 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.52
PhyloP100		0.34
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: rs1859767; hg19: chr7-108088323;