rs1269627

Variant names:

• chr7-108224507-C-T
• rs1269627
• NM_001037132.4:c.779-671G>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.779-671G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,002 control chromosomes in the GnomAD database, including 46,733 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 0.78 (46733 hom., cov: 32)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.779-671G>A		intron_variant	Intron 10 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.779-671G>A		intron_variant	Intron 10 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118976 AN: 151884 Hom.: 46712 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.783 AC: 119054 AN: 152002 Hom.: 46733 Cov.: 32 AF XY: 0.785 AC XY: 58305 AN XY: 74282

African (AFR) AF: 0.767 AC: 31830 AN: 41478

American (AMR) AF: 0.826 AC: 12625 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2699 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4480 AN: 5176

South Asian (SAS) AF: 0.696 AC: 3352 AN: 4816

European-Finnish (FIN) AF: 0.785 AC: 8289 AN: 10562

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.783 AC: 53160 AN: 67894

Other (OTH) AF: 0.773 AC: 1632 AN: 2112

Alfa AF: 0.777 Hom.: 21948

Bravo AF: 0.788

Asia WGS AF: 0.760 AC: 2635 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.019
DANN	Benign	0.42
PhyloP100		-2.3
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: rs1269627; hg19: chr7-107864951;