chr3-3042969-C-T

Variant names:

• chr3-3042969-C-T
• rs6800354
• NM_175607.3:c.2512-8C>T

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.2512-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,609,488 control chromosomes in the GnomAD database, including 44,952 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 0.25 (5144 hom., cov: 33)
  • Exomes 𝑓: 0.23 (39808 hom.)
• Consequence: CNTN4 NM_175607.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001856
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00500
• Publications: 6 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=-0.58).
• BP6: Variant 3-3042969-C-T is Benign according to our data. Variant chr3-3042969-C-T is described in ClinVar as Benign. ClinVar VariationId is 1242402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 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.2512-8C>T		splice_region intron	N/A	NP_783200.1	Q8IWV2-1
	CNTN4	NM_001206955.2		c.2512-8C>T		splice_region intron	N/A	NP_001193884.1	Q8IWV2-1
	CNTN4	NM_001350095.2		c.2512-8C>T		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.2512-8C>T		splice_region intron	N/A	ENSP00000396010.1	Q8IWV2-1
	CNTN4	ENST00000397459.6	TSL:1	c.1528-8C>T		splice_region intron	N/A	ENSP00000380600.2	Q8IWV2-4
	CNTN4	ENST00000484686.1	TSL:1	n.762-8C>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38293 AN: 151916 Hom.: 5130 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.265

GnomAD2 exomes AF: 0.216 AC: 54074 AN: 249844 AF XY: 0.214

Gnomad AFR exome AF: 0.322

Gnomad AMR exome AF: 0.185

Gnomad ASJ exome AF: 0.215

Gnomad EAS exome AF: 0.109

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.241

Gnomad OTH exome AF: 0.245

GnomAD4 exome AF: 0.231 AC: 336726 AN: 1457454 Hom.: 39808 Cov.: 31 AF XY: 0.229 AC XY: 166352 AN XY: 725340

African (AFR) AF: 0.326 AC: 10872 AN: 33362

American (AMR) AF: 0.191 AC: 8523 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 5563 AN: 26100

East Asian (EAS) AF: 0.127 AC: 5025 AN: 39664

South Asian (SAS) AF: 0.180 AC: 15535 AN: 86110

European-Finnish (FIN) AF: 0.208 AC: 11080 AN: 53388

Middle Eastern (MID) AF: 0.304 AC: 1751 AN: 5762

European-Non Finnish (NFE) AF: 0.238 AC: 264088 AN: 1108142

Other (OTH) AF: 0.237 AC: 14289 AN: 60270

GnomAD4 genome AF: 0.252 AC: 38336 AN: 152034 Hom.: 5144 Cov.: 33 AF XY: 0.249 AC XY: 18497 AN XY: 74322

African (AFR) AF: 0.318 AC: 13186 AN: 41430

American (AMR) AF: 0.235 AC: 3586 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3470

East Asian (EAS) AF: 0.113 AC: 586 AN: 5170

South Asian (SAS) AF: 0.165 AC: 796 AN: 4818

European-Finnish (FIN) AF: 0.207 AC: 2195 AN: 10580

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16274 AN: 67964

Other (OTH) AF: 0.268 AC: 565 AN: 2108

Alfa AF: 0.248 Hom.: 3811

Bravo AF: 0.259

Asia WGS AF: 0.148 AC: 513 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	-0.58
CADD	Benign	9.9
DANN	Benign	0.81
PhyloP100		-0.0050
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.010
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: rs6800354; hg19: chr3-3084653; COSMIC: COSV61878206;