3-2592603-C-T

Variant names:

• chr3-2592603-C-T
• rs73110658
• NM_175607.3:c.55+21045C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_175607.3(CNTN4):​c.55+21045C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 152,198 control chromosomes in the GnomAD database, including 370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.066 (370 hom., cov: 33)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.305
• 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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-2592603-C-T is Benign according to our data. Variant chr3-2592603-C-T is described in ClinVar as [Benign]. Clinvar id is 1291781.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.55+21045C>T		intron_variant	Intron 4 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.55+21045C>T		intron_variant	Intron 4 of 24	5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9956 AN: 152080 Hom.: 370 Cov.: 33

Gnomad AFR AF: 0.0755

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0767

Gnomad ASJ AF: 0.0557

Gnomad EAS AF: 0.0702

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0897

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.0784

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0655 AC: 9969 AN: 152198 Hom.: 370 Cov.: 33 AF XY: 0.0698 AC XY: 5192 AN XY: 74420

African (AFR) AF: 0.0754 AC: 3132 AN: 41544

American (AMR) AF: 0.0770 AC: 1176 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0557 AC: 193 AN: 3468

East Asian (EAS) AF: 0.0702 AC: 362 AN: 5160

South Asian (SAS) AF: 0.136 AC: 654 AN: 4818

European-Finnish (FIN) AF: 0.0897 AC: 950 AN: 10590

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0487 AC: 3313 AN: 68020

Other (OTH) AF: 0.0785 AC: 166 AN: 2114

Alfa AF: 0.0563 Hom.: 424

Bravo AF: 0.0634

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.43
PhyloP100		0.30
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: rs73110658; hg19: chr3-2634287;