3-3040066-A-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_175607.3(CNTN4):​c.2193A>T​(p.Arg731Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,611,044 control chromosomes in the GnomAD database, including 138,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9959 hom., cov: 34)
  • Exomes 𝑓: 0.41 (128079 hom.)
• Consequence: CNTN4 NM_175607.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.441
• Publications: 19 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 3-3040066-A-T is Benign according to our data. Variant chr3-3040066-A-T is described in ClinVar as Benign. ClinVar VariationId is 1286695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.441 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

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>T	p.Arg731Arg	synonymous	Exon 20 of 25	NP_783200.1	Q8IWV2-1
	CNTN4	NM_001206955.2		c.2193A>T	p.Arg731Arg	synonymous	Exon 19 of 24	NP_001193884.1	Q8IWV2-1
	CNTN4	NM_001350095.2		c.2193A>T	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>T	p.Arg731Arg	synonymous	Exon 20 of 25	ENSP00000396010.1	Q8IWV2-1
	CNTN4	ENST00000397459.6	TSL:1	c.1209A>T	p.Arg403Arg	synonymous	Exon 11 of 16	ENSP00000380600.2	Q8IWV2-4
	CNTN4	ENST00000484686.1	TSL:1	n.443A>T		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51220 AN: 152026 Hom.: 9961 Cov.: 34

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.353

GnomAD2 exomes AF: 0.408 AC: 102506 AN: 251420 AF XY: 0.414

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.275

Gnomad EAS exome AF: 0.564

Gnomad FIN exome AF: 0.388

Gnomad NFE exome AF: 0.416

Gnomad OTH exome AF: 0.376

GnomAD4 exome AF: 0.413 AC: 602697 AN: 1458900 Hom.: 128079 Cov.: 35 AF XY: 0.415 AC XY: 301062 AN XY: 725976

African (AFR) AF: 0.119 AC: 3971 AN: 33448

American (AMR) AF: 0.435 AC: 19461 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 7297 AN: 26118

East Asian (EAS) AF: 0.587 AC: 23280 AN: 39690

South Asian (SAS) AF: 0.457 AC: 39419 AN: 86186

European-Finnish (FIN) AF: 0.389 AC: 20778 AN: 53418

Middle Eastern (MID) AF: 0.305 AC: 1759 AN: 5764

European-Non Finnish (NFE) AF: 0.418 AC: 463667 AN: 1109254

Other (OTH) AF: 0.383 AC: 23065 AN: 60300

GnomAD4 genome AF: 0.337 AC: 51212 AN: 152144 Hom.: 9959 Cov.: 34 AF XY: 0.339 AC XY: 25191 AN XY: 74362

African (AFR) AF: 0.137 AC: 5684 AN: 41538

American (AMR) AF: 0.383 AC: 5860 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1031 AN: 3470

East Asian (EAS) AF: 0.578 AC: 2980 AN: 5156

South Asian (SAS) AF: 0.467 AC: 2252 AN: 4826

European-Finnish (FIN) AF: 0.390 AC: 4127 AN: 10574

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28104 AN: 67966

Other (OTH) AF: 0.348 AC: 735 AN: 2114

Alfa AF: 0.375 Hom.: 3681

Bravo AF: 0.326

Asia WGS AF: 0.467 AC: 1626 AN: 3478

EpiCase AF: 0.393

EpiControl AF: 0.399

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.8
DANN	Benign	0.72
PhyloP100		0.44
Mutation Taster		=98/2	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: rs6802588; hg19: chr3-3081750; COSMIC: COSV61869898; COSMIC: COSV61869898;