NM_175607.3:c.2398+48T>A

Variant names:

• chr3-3040319-T-A
• rs339283
• NM_175607.3:c.2398+48T>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+48T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,391,810 control chromosomes in the GnomAD database, including 13,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2890 hom., cov: 34)
  • Exomes 𝑓: 0.13 (10833 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.451
• Publications: 2 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=-0.79).
• BP6: Variant 3-3040319-T-A is Benign according to our data. Variant chr3-3040319-T-A is described in ClinVar as Benign. ClinVar VariationId is 1262848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 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+48T>A		intron	N/A	NP_783200.1	Q8IWV2-1
	CNTN4	NM_001206955.2		c.2398+48T>A		intron	N/A	NP_001193884.1	Q8IWV2-1
	CNTN4	NM_001350095.2		c.2398+48T>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+48T>A		intron	N/A	ENSP00000396010.1	Q8IWV2-1
	CNTN4	ENST00000397459.6	TSL:1	c.1414+48T>A		intron	N/A	ENSP00000380600.2	Q8IWV2-4
	CNTN4	ENST00000484686.1	TSL:1	n.648+48T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26774 AN: 152118 Hom.: 2882 Cov.: 34

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.169

GnomAD2 exomes AF: 0.135 AC: 32728 AN: 242260 AF XY: 0.132

Gnomad AFR exome AF: 0.317

Gnomad AMR exome AF: 0.0912

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.184

Gnomad FIN exome AF: 0.0930

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.125 AC: 155128 AN: 1239574 Hom.: 10833 Cov.: 17 AF XY: 0.125 AC XY: 78225 AN XY: 627476

African (AFR) AF: 0.307 AC: 8871 AN: 28878

American (AMR) AF: 0.0936 AC: 4114 AN: 43962

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 4969 AN: 24690

East Asian (EAS) AF: 0.157 AC: 6043 AN: 38592

South Asian (SAS) AF: 0.101 AC: 8224 AN: 81612

European-Finnish (FIN) AF: 0.0893 AC: 4603 AN: 51534

Middle Eastern (MID) AF: 0.176 AC: 929 AN: 5270

European-Non Finnish (NFE) AF: 0.121 AC: 110075 AN: 911932

Other (OTH) AF: 0.137 AC: 7300 AN: 53104

GnomAD4 genome AF: 0.176 AC: 26814 AN: 152236 Hom.: 2890 Cov.: 34 AF XY: 0.173 AC XY: 12906 AN XY: 74416

African (AFR) AF: 0.305 AC: 12685 AN: 41524

American (AMR) AF: 0.139 AC: 2131 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3470

East Asian (EAS) AF: 0.167 AC: 866 AN: 5176

South Asian (SAS) AF: 0.103 AC: 498 AN: 4826

European-Finnish (FIN) AF: 0.0906 AC: 961 AN: 10608

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.126 AC: 8569 AN: 68022

Other (OTH) AF: 0.167 AC: 354 AN: 2116

Alfa AF: 0.157 Hom.: 373

Bravo AF: 0.187

Asia WGS AF: 0.120 AC: 419 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	-0.79
CADD	Benign	2.2
DANN	Benign	0.63
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs339283; hg19: chr3-3082003;