NM_175607.3:c.2398+4T>C

Variant names:

• chr3-3040275-T-C
• rs339284
• NM_175607.3:c.2398+4T>C

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+4T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 1,579,766 control chromosomes in the GnomAD database, including 9,346 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2082 hom., cov: 34)
  • Exomes 𝑓: 0.094 (7264 hom.)
• Consequence: CNTN4 NM_175607.3 splice_region, intron
• Scores: Splicing: ADA: 0.00003434
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.483
• Publications: 9 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=-0.88).
• BP6: Variant 3-3040275-T-C is Benign according to our data. Variant chr3-3040275-T-C is described in ClinVar as Benign. ClinVar VariationId is 1221661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 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+4T>C		splice_region intron	N/A	NP_783200.1	Q8IWV2-1
	CNTN4	NM_001206955.2		c.2398+4T>C		splice_region intron	N/A	NP_001193884.1	Q8IWV2-1
	CNTN4	NM_001350095.2		c.2398+4T>C		splice_region 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+4T>C		splice_region intron	N/A	ENSP00000396010.1	Q8IWV2-1
	CNTN4	ENST00000397459.6	TSL:1	c.1414+4T>C		splice_region intron	N/A	ENSP00000380600.2	Q8IWV2-4
	CNTN4	ENST00000484686.1	TSL:1	n.648+4T>C		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21143 AN: 152198 Hom.: 2076 Cov.: 34

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.0486

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0936

Gnomad OTH AF: 0.130

GnomAD2 exomes AF: 0.0893 AC: 22416 AN: 251102 AF XY: 0.0865

Gnomad AFR exome AF: 0.283

Gnomad AMR exome AF: 0.0622

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.00147

Gnomad FIN exome AF: 0.0523

Gnomad NFE exome AF: 0.0911

Gnomad OTH exome AF: 0.0976

GnomAD4 exome AF: 0.0942 AC: 134410 AN: 1427450 Hom.: 7264 Cov.: 27 AF XY: 0.0929 AC XY: 66186 AN XY: 712454

African (AFR) AF: 0.284 AC: 9367 AN: 32958

American (AMR) AF: 0.0662 AC: 2959 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 3914 AN: 25902

East Asian (EAS) AF: 0.000607 AC: 24 AN: 39514

South Asian (SAS) AF: 0.0679 AC: 5805 AN: 85546

European-Finnish (FIN) AF: 0.0511 AC: 2728 AN: 53350

Middle Eastern (MID) AF: 0.119 AC: 681 AN: 5706

European-Non Finnish (NFE) AF: 0.0952 AC: 102872 AN: 1080524

Other (OTH) AF: 0.102 AC: 6060 AN: 59264

GnomAD4 genome AF: 0.139 AC: 21172 AN: 152316 Hom.: 2082 Cov.: 34 AF XY: 0.134 AC XY: 10014 AN XY: 74484

African (AFR) AF: 0.276 AC: 11468 AN: 41552

American (AMR) AF: 0.110 AC: 1691 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5184

South Asian (SAS) AF: 0.0604 AC: 292 AN: 4832

European-Finnish (FIN) AF: 0.0486 AC: 517 AN: 10630

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

European-Non Finnish (NFE) AF: 0.0936 AC: 6367 AN: 68024

Other (OTH) AF: 0.128 AC: 271 AN: 2114

Alfa AF: 0.113 Hom.: 2214

Bravo AF: 0.148

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CNTN4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.54
DANN	Benign	0.60
PhyloP100		-0.48
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000034
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.010		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: rs339284; hg19: chr3-3081959;