7-108230187-A-G

Variant names:

• chr7-108230187-A-G
• rs1269629
• NM_001037132.4:c.550+844T>C

Variant summary

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

The NM_001037132.4(NRCAM):​c.550+844T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,684 control chromosomes in the GnomAD database, including 13,975 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 0.40 (13975 hom., cov: 30)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.550+844T>C		intron_variant	Intron 8 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.550+844T>C		intron_variant	Intron 8 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60138 AN: 151564 Hom.: 13984 Cov.: 30

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.396 AC: 60135 AN: 151684 Hom.: 13975 Cov.: 30 AF XY: 0.404 AC XY: 29891 AN XY: 74052

African (AFR) AF: 0.167 AC: 6904 AN: 41356

American (AMR) AF: 0.543 AC: 8262 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1857 AN: 3468

East Asian (EAS) AF: 0.828 AC: 4244 AN: 5126

South Asian (SAS) AF: 0.483 AC: 2319 AN: 4804

European-Finnish (FIN) AF: 0.419 AC: 4388 AN: 10466

Middle Eastern (MID) AF: 0.493 AC: 143 AN: 290

European-Non Finnish (NFE) AF: 0.450 AC: 30574 AN: 67934

Other (OTH) AF: 0.416 AC: 876 AN: 2108

Alfa AF: 0.445 Hom.: 13264

Bravo AF: 0.399

Asia WGS AF: 0.585 AC: 2032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.10
DANN	Benign	0.53
PhyloP100		-1.1
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: rs1269629; hg19: chr7-107870631;