rs414077

Variant names:

• chr7-108180467-G-T
• rs414077
• NM_001037132.4:c.2647-40C>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.2647-40C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 1,520,280 control chromosomes in the GnomAD database, including 628,355 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 0.91 (62976 hom., cov: 34)
  • Exomes 𝑓: 0.91 (565379 hom.)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 3 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 = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.2647-40C>A		intron_variant	Intron 24 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.2647-40C>A		intron_variant	Intron 24 of 32	5	NM_001037132.4	ENSP00000368314.3
NRCAM	ENST00000379024.8	c.2590-40C>A		intron_variant	Intron 23 of 29	1		ENSP00000368310.4
NRCAM	ENST00000351718.8	c.2599-40C>A		intron_variant	Intron 22 of 27	1		ENSP00000325269.6
NRCAM	ENST00000413765.6	c.2647-40C>A		intron_variant	Intron 24 of 30	2		ENSP00000407858.3

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138381 AN: 152192 Hom.: 62927 Cov.: 34

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.907

GnomAD2 exomes AF: 0.919 AC: 225666 AN: 245556 AF XY: 0.917

Gnomad AFR exome AF: 0.900

Gnomad AMR exome AF: 0.952

Gnomad ASJ exome AF: 0.924

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.922

Gnomad NFE exome AF: 0.904

Gnomad OTH exome AF: 0.921

GnomAD4 exome AF: 0.909 AC: 1243405 AN: 1367970 Hom.: 565379 Cov.: 19 AF XY: 0.908 AC XY: 623043 AN XY: 685950

African (AFR) AF: 0.896 AC: 28219 AN: 31510

American (AMR) AF: 0.948 AC: 41770 AN: 44072

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 23548 AN: 25458

East Asian (EAS) AF: 1.00 AC: 39174 AN: 39186

South Asian (SAS) AF: 0.897 AC: 75080 AN: 83736

European-Finnish (FIN) AF: 0.923 AC: 48778 AN: 52822

Middle Eastern (MID) AF: 0.871 AC: 4900 AN: 5626

European-Non Finnish (NFE) AF: 0.904 AC: 929734 AN: 1028312

Other (OTH) AF: 0.912 AC: 52202 AN: 57248

GnomAD4 genome AF: 0.909 AC: 138488 AN: 152310 Hom.: 62976 Cov.: 34 AF XY: 0.910 AC XY: 67798 AN XY: 74480

African (AFR) AF: 0.896 AC: 37239 AN: 41560

American (AMR) AF: 0.926 AC: 14155 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3238 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5176 AN: 5180

South Asian (SAS) AF: 0.895 AC: 4320 AN: 4826

European-Finnish (FIN) AF: 0.924 AC: 9815 AN: 10626

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61536 AN: 68032

Other (OTH) AF: 0.908 AC: 1921 AN: 2116

Alfa AF: 0.905 Hom.: 97016

Bravo AF: 0.909

Asia WGS AF: 0.951 AC: 3307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.95
DANN	Benign	0.70
PhyloP100		-0.29
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: rs414077; hg19: chr7-107820911;