chr7-108159846-A-C

Variant names:

• chr7-108159846-A-C
• rs427615
• NM_001037132.4:c.3599-305T>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.3599-305T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 151,956 control chromosomes in the GnomAD database, including 44,899 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 0.76 (44899 hom., cov: 32)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461
• Publications: 0 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.3599-305T>G		intron_variant	Intron 31 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.3599-305T>G		intron_variant	Intron 31 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115275 AN: 151840 Hom.: 44894 Cov.: 32

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.759 AC: 115331 AN: 151956 Hom.: 44899 Cov.: 32 AF XY: 0.756 AC XY: 56137 AN XY: 74270

African (AFR) AF: 0.567 AC: 23497 AN: 41428

American (AMR) AF: 0.824 AC: 12579 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3094 AN: 3470

East Asian (EAS) AF: 0.833 AC: 4309 AN: 5170

South Asian (SAS) AF: 0.724 AC: 3472 AN: 4796

European-Finnish (FIN) AF: 0.757 AC: 7988 AN: 10554

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57719 AN: 67964

Other (OTH) AF: 0.772 AC: 1628 AN: 2110

Alfa AF: 0.791 Hom.: 6286

Bravo AF: 0.757

Asia WGS AF: 0.774 AC: 2685 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.68
PhyloP100		-0.46
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: rs427615; hg19: chr7-107800291;