NM_175607.3:c.2398+181G>A

Variant names:

• chr3-3040452-G-A
• rs235145
• NM_175607.3:c.2398+181G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_175607.3(CNTN4):​c.2398+181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 644,360 control chromosomes in the GnomAD database, including 4,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2171 hom., cov: 33)
  • Exomes 𝑓: 0.088 (2480 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.78
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 3-3040452-G-A is Benign according to our data. Variant chr3-3040452-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 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.2398+181G>A		intron	N/A	NP_783200.1	Q8IWV2-1
	CNTN4	NM_001206955.2		c.2398+181G>A		intron	N/A	NP_001193884.1	Q8IWV2-1
	CNTN4	NM_001350095.2		c.2398+181G>A		intron	N/A	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.2398+181G>A		intron	N/A	ENSP00000396010.1	Q8IWV2-1
	CNTN4	ENST00000397459.6	TSL:1	c.1414+181G>A		intron	N/A	ENSP00000380600.2	Q8IWV2-4
	CNTN4	ENST00000484686.1	TSL:1	n.648+181G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21480 AN: 152056 Hom.: 2162 Cov.: 33

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0603

Gnomad FIN AF: 0.0486

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0936

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.0884 AC: 43521 AN: 492186 Hom.: 2480 AF XY: 0.0871 AC XY: 22791 AN XY: 261696

African (AFR) AF: 0.285 AC: 4065 AN: 14286

American (AMR) AF: 0.0696 AC: 2147 AN: 30842

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 2438 AN: 16636

East Asian (EAS) AF: 0.000555 AC: 17 AN: 30638

South Asian (SAS) AF: 0.0670 AC: 3604 AN: 53804

European-Finnish (FIN) AF: 0.0497 AC: 1502 AN: 30248

Middle Eastern (MID) AF: 0.129 AC: 275 AN: 2134

European-Non Finnish (NFE) AF: 0.0930 AC: 26602 AN: 285890

Other (OTH) AF: 0.104 AC: 2871 AN: 27708

GnomAD4 genome AF: 0.141 AC: 21521 AN: 152174 Hom.: 2171 Cov.: 33 AF XY: 0.137 AC XY: 10194 AN XY: 74376

African (AFR) AF: 0.285 AC: 11806 AN: 41492

American (AMR) AF: 0.111 AC: 1703 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 457 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.0605 AC: 292 AN: 4824

European-Finnish (FIN) AF: 0.0486 AC: 515 AN: 10596

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0936 AC: 6366 AN: 68002

Other (OTH) AF: 0.129 AC: 274 AN: 2116

Alfa AF: 0.123 Hom.: 177

Bravo AF: 0.151

Asia WGS AF: 0.0430 AC: 150 AN: 3478

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	-0.97
CADD	Benign	0.94
DANN	Benign	0.79
PhyloP100		-1.8
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: rs235145; hg19: chr3-3082136; COSMIC: COSV61873772; COSMIC: COSV61873772;