3-3039860-C-T

Variant names:

• chr3-3039860-C-T
• rs339286
• NM_175607.3:c.2164-177C>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.2164-177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 642,042 control chromosomes in the GnomAD database, including 5,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2881 hom., cov: 33)
  • Exomes 𝑓: 0.092 (2825 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.338
• Publications: 7 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=-0.87).
• BP6: Variant 3-3039860-C-T is Benign according to our data. Variant chr3-3039860-C-T is described in ClinVar as Benign. ClinVar VariationId is 1278521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 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.2164-177C>T		intron	N/A	NP_783200.1	Q8IWV2-1
	CNTN4	NM_001206955.2		c.2164-177C>T		intron	N/A	NP_001193884.1	Q8IWV2-1
	CNTN4	NM_001350095.2		c.2164-177C>T		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.2164-177C>T		intron	N/A	ENSP00000396010.1	Q8IWV2-1
	CNTN4	ENST00000397459.6	TSL:1	c.1180-177C>T		intron	N/A	ENSP00000380600.2	Q8IWV2-4
	CNTN4	ENST00000484686.1	TSL:1	n.237C>T		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23822 AN: 152036 Hom.: 2870 Cov.: 33

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.0499

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0940

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.0917 AC: 44932 AN: 489890 Hom.: 2825 Cov.: 4 AF XY: 0.0900 AC XY: 23708 AN XY: 263400

African (AFR) AF: 0.339 AC: 4874 AN: 14386

American (AMR) AF: 0.0737 AC: 2256 AN: 30620

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 2455 AN: 16396

East Asian (EAS) AF: 0.000475 AC: 14 AN: 29490

South Asian (SAS) AF: 0.0684 AC: 3687 AN: 53928

European-Finnish (FIN) AF: 0.0508 AC: 1638 AN: 32262

Middle Eastern (MID) AF: 0.129 AC: 310 AN: 2410

European-Non Finnish (NFE) AF: 0.0946 AC: 26785 AN: 283086

Other (OTH) AF: 0.107 AC: 2913 AN: 27312

GnomAD4 genome AF: 0.157 AC: 23867 AN: 152152 Hom.: 2881 Cov.: 33 AF XY: 0.152 AC XY: 11302 AN XY: 74380

African (AFR) AF: 0.337 AC: 13980 AN: 41462

American (AMR) AF: 0.118 AC: 1801 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3472

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5178

South Asian (SAS) AF: 0.0606 AC: 292 AN: 4822

European-Finnish (FIN) AF: 0.0499 AC: 528 AN: 10588

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0940 AC: 6393 AN: 68020

Other (OTH) AF: 0.144 AC: 305 AN: 2116

Alfa AF: 0.114 Hom.: 2437

Bravo AF: 0.169

Asia WGS AF: 0.0470 AC: 162 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	-0.87
CADD	Benign	5.5
DANN	Benign	0.51
PhyloP100		0.34
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: rs339286; hg19: chr3-3081544;