rs381828

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-108168522-A-C
• chr7-108168522-A-G
• chr7-108168522-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037132.4(NRCAM):​c.3188-120T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 906,352 control chromosomes in the GnomAD database, including 305,192 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 0.72 (42032 hom., cov: 33)
  • Exomes 𝑓: 0.83 (263160 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.3188-120T>G		intron_variant	Intron 28 of 32	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.3188-120T>G		intron_variant	Intron 28 of 32	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109844 AN: 152002 Hom.: 42039 Cov.: 33

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.738

GnomAD4 exome AF: 0.832 AC: 627405 AN: 754232 Hom.: 263160 AF XY: 0.832 AC XY: 305998 AN XY: 367836

African (AFR) AF: 0.427 AC: 6964 AN: 16292

American (AMR) AF: 0.808 AC: 7101 AN: 8788

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 10986 AN: 12448

East Asian (EAS) AF: 0.796 AC: 19424 AN: 24396

South Asian (SAS) AF: 0.722 AC: 15165 AN: 21000

European-Finnish (FIN) AF: 0.786 AC: 18995 AN: 24162

Middle Eastern (MID) AF: 0.766 AC: 2229 AN: 2910

European-Non Finnish (NFE) AF: 0.850 AC: 519784 AN: 611278

Other (OTH) AF: 0.812 AC: 26757 AN: 32958

GnomAD4 genome AF: 0.722 AC: 109872 AN: 152120 Hom.: 42032 Cov.: 33 AF XY: 0.720 AC XY: 53521 AN XY: 74370

African (AFR) AF: 0.446 AC: 18494 AN: 41468

American (AMR) AF: 0.804 AC: 12291 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3080 AN: 3472

East Asian (EAS) AF: 0.834 AC: 4324 AN: 5184

South Asian (SAS) AF: 0.712 AC: 3435 AN: 4824

European-Finnish (FIN) AF: 0.757 AC: 8002 AN: 10570

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57654 AN: 68008

Other (OTH) AF: 0.737 AC: 1552 AN: 2106

Alfa AF: 0.778 Hom.: 5916

Bravo AF: 0.715

Asia WGS AF: 0.759 AC: 2640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.6
DANN	Benign	0.50
PhyloP100		0.55
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: rs381828; hg19: chr7-107808967;