chr7-108184445-C-G

Variant names:

• chr7-108184445-C-G
• rs401433
• NM_001037132.4:c.2205G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001037132.4(NRCAM):​c.2205G>C​(p.Ala735Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,613,832 control chromosomes in the GnomAD database, including 472,088 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 0.68 (37216 hom., cov: 33)
  • Exomes 𝑓: 0.77 (434872 hom.)
• Consequence: NRCAM NM_001037132.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 24 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-2.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRCAM	NM_001037132.4	MANE Select	c.2205G>C	p.Ala735Ala	synonymous	Exon 21 of 33	NP_001032209.1	Q92823-1
	NRCAM	NM_001371156.1		c.2205G>C	p.Ala735Ala	synonymous	Exon 21 of 33	NP_001358085.1
	NRCAM	NM_001371131.1		c.2205G>C	p.Ala735Ala	synonymous	Exon 22 of 34	NP_001358060.1	Q92823-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRCAM	ENST00000379028.8	TSL:5 MANE Select	c.2205G>C	p.Ala735Ala	synonymous	Exon 21 of 33	ENSP00000368314.3	Q92823-1
	NRCAM	ENST00000379024.8	TSL:1	c.2148G>C	p.Ala716Ala	synonymous	Exon 20 of 30	ENSP00000368310.4	Q92823-6
	NRCAM	ENST00000351718.8	TSL:1	c.2157G>C	p.Ala719Ala	synonymous	Exon 19 of 28	ENSP00000325269.6	Q92823-4

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103367 AN: 152014 Hom.: 37206 Cov.: 33

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.685

GnomAD2 exomes AF: 0.760 AC: 190785 AN: 251116 AF XY: 0.761

Gnomad AFR exome AF: 0.422

Gnomad AMR exome AF: 0.827

Gnomad ASJ exome AF: 0.710

Gnomad EAS exome AF: 0.971

Gnomad FIN exome AF: 0.750

Gnomad NFE exome AF: 0.768

Gnomad OTH exome AF: 0.755

GnomAD4 exome AF: 0.768 AC: 1122989 AN: 1461700 Hom.: 434872 Cov.: 54 AF XY: 0.768 AC XY: 558128 AN XY: 727174

African (AFR) AF: 0.416 AC: 13918 AN: 33476

American (AMR) AF: 0.817 AC: 36531 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 18562 AN: 26134

East Asian (EAS) AF: 0.951 AC: 37768 AN: 39700

South Asian (SAS) AF: 0.734 AC: 63327 AN: 86246

European-Finnish (FIN) AF: 0.755 AC: 40313 AN: 53370

Middle Eastern (MID) AF: 0.618 AC: 3564 AN: 5768

European-Non Finnish (NFE) AF: 0.777 AC: 863733 AN: 1111894

Other (OTH) AF: 0.750 AC: 45273 AN: 60392

GnomAD4 genome AF: 0.680 AC: 103411 AN: 152132 Hom.: 37216 Cov.: 33 AF XY: 0.683 AC XY: 50825 AN XY: 74376

African (AFR) AF: 0.428 AC: 17765 AN: 41474

American (AMR) AF: 0.769 AC: 11750 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2509 AN: 3470

East Asian (EAS) AF: 0.960 AC: 4973 AN: 5180

South Asian (SAS) AF: 0.735 AC: 3548 AN: 4826

European-Finnish (FIN) AF: 0.746 AC: 7885 AN: 10576

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52570 AN: 68008

Other (OTH) AF: 0.688 AC: 1451 AN: 2110

Alfa AF: 0.744 Hom.: 13910

Bravo AF: 0.672

Asia WGS AF: 0.796 AC: 2767 AN: 3478

EpiCase AF: 0.767

EpiControl AF: 0.760

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.028
DANN	Benign	0.44
PhyloP100		-2.2
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: rs401433; hg19: chr7-107824889; COSMIC: COSV105261822;