7-108168522-A-T

Variant names:

• chr7-108168522-A-T
• rs381828
• NM_001037132.4:c.3188-120T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001037132.4(NRCAM):​c.3188-120T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000265 in 755,846 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: NRCAM NM_001037132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545
• Publications: 4 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

LOC102724363 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.3188-120T>A		intron	N/A	NP_001032209.1	Q92823-1
	NRCAM	NM_001371156.1		c.3197-120T>A		intron	N/A	NP_001358085.1
	NRCAM	NM_001371131.1		c.3188-120T>A		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.3188-120T>A		intron	N/A	ENSP00000368314.3	Q92823-1
	NRCAM	ENST00000379024.8	TSL:1	c.3130+6800T>A		intron	N/A	ENSP00000368310.4	Q92823-6
	NRCAM	ENST00000351718.8	TSL:1	c.3103+7908T>A		intron	N/A	ENSP00000325269.6	Q92823-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000265 AC: 2 AN: 755846 Hom.: 0 AF XY: 0.00000271 AC XY: 1 AN XY: 368612

African (AFR) AF: 0.00 AC: 0 AN: 16354

American (AMR) AF: 0.00 AC: 0 AN: 8812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12456

East Asian (EAS) AF: 0.00 AC: 0 AN: 24446

South Asian (SAS) AF: 0.00 AC: 0 AN: 21078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2920

European-Non Finnish (NFE) AF: 0.00000327 AC: 2 AN: 612536

Other (OTH) AF: 0.00 AC: 0 AN: 33030

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.5
DANN	Benign	0.50
PhyloP100		0.55

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: rs381828; hg19: chr7-107808967;