7-108209223-T-C

Variant names:

• chr7-108209223-T-C
• rs1269620
• NM_001037132.4:c.1075+198A>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.1075+198A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.982 in 152,266 control chromosomes in the GnomAD database, including 73,465 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 0.98 (73465 hom., cov: 32)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 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.1075+198A>G		intron	N/A	NP_001032209.1	Q92823-1
	NRCAM	NM_001371156.1		c.1075+198A>G		intron	N/A	NP_001358085.1
	NRCAM	NM_001371131.1		c.1075+198A>G		intron	N/A	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.1075+198A>G		intron	N/A	ENSP00000368314.3	Q92823-1
	NRCAM	ENST00000379024.8	TSL:1	c.1018+198A>G		intron	N/A	ENSP00000368310.4	Q92823-6
	NRCAM	ENST00000351718.8	TSL:1	c.1057+198A>G		intron	N/A	ENSP00000325269.6	Q92823-4

Frequencies

GnomAD3 genomes AF: 0.982 AC: 149459 AN: 152148 Hom.: 73406 Cov.: 32

Gnomad AFR AF: 0.995

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.997

Gnomad FIN AF: 0.973

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.989

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

GnomAD4 genome AF: 0.982 AC: 149577 AN: 152266 Hom.: 73465 Cov.: 32 AF XY: 0.983 AC XY: 73160 AN XY: 74446

African (AFR) AF: 0.995 AC: 41327 AN: 41552

American (AMR) AF: 0.983 AC: 15035 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3456 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5177 AN: 5178

South Asian (SAS) AF: 0.997 AC: 4802 AN: 4818

European-Finnish (FIN) AF: 0.973 AC: 10321 AN: 10612

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.973 AC: 66173 AN: 68020

Other (OTH) AF: 0.989 AC: 2089 AN: 2112

Alfa AF: 0.979 Hom.: 13408

Bravo AF: 0.984

Asia WGS AF: 0.997 AC: 3462 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.4
DANN	Benign	0.77
PhyloP100		-0.12
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: rs1269620; hg19: chr7-107849667;