3-3040066-A-C

Variant names:

• chr3-3040066-A-C
• rs6802588
• NM_175607.3:c.2193A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_175607.3(CNTN4):​c.2193A>C​(p.Arg731Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,254 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. Synonymous variant affecting the same amino acid position (i.e. R731R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CNTN4 NM_175607.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441
• Publications: 0 publications found

Genes affected

CNTN4 (HGNC:2174): (contactin 4) This gene encodes a member of the contactin family of immunoglobulins. Contactins are axon-associated cell adhesion molecules that function in neuronal network formation and plasticity. The encoded protein is a glycosylphosphatidylinositol-anchored neuronal membrane protein that may play a role in the formation of axon connections in the developing nervous system. Deletion or mutation of this gene may play a role in 3p deletion syndrome and autism spectrum disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

CNTN4-AS1 (HGNC:39985): (CNTN4 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.441 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175607.3. 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
	CNTN4	NM_175607.3	MANE Select	c.2193A>C	p.Arg731Arg	synonymous	Exon 20 of 25	NP_783200.1	Q8IWV2-1
	CNTN4	NM_001206955.2		c.2193A>C	p.Arg731Arg	synonymous	Exon 19 of 24	NP_001193884.1	Q8IWV2-1
	CNTN4	NM_001350095.2		c.2193A>C	p.Arg731Arg	synonymous	Exon 20 of 25	NP_001337024.1	Q8IWV2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	ENST00000418658.6	TSL:5 MANE Select	c.2193A>C	p.Arg731Arg	synonymous	Exon 20 of 25	ENSP00000396010.1	Q8IWV2-1
	CNTN4	ENST00000397459.6	TSL:1	c.1209A>C	p.Arg403Arg	synonymous	Exon 11 of 16	ENSP00000380600.2	Q8IWV2-4
	CNTN4	ENST00000484686.1	TSL:1	n.443A>C		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461254 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 727016

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111426

Other (OTH) AF: 0.0000166 AC: 1 AN: 60376

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.6
DANN	Benign	0.70
PhyloP100		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6802588; hg19: chr3-3081750;