3-3042595-C-T

Position:

• chr3-3042595-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_175607.3(CNTN4):​c.2511+173C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,084 control chromosomes in the GnomAD database, including 4,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (4903 hom., cov: 33)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.233

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-3042595-C-T is Benign according to our data. Variant chr3-3042595-C-T is described in ClinVar as [Benign]. Clinvar id is 1222103.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.2511+173C>T		intron_variant		ENST00000418658.6	NP_783200.1
CNTN4-AS1	NR_046554.1	n.180+318G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.2511+173C>T		intron_variant		5	NM_175607.3	ENSP00000396010	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37489 AN: 151966 Hom.: 4889 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.247 AC: 37530 AN: 152084 Hom.: 4903 Cov.: 33 AF XY: 0.244 AC XY: 18107 AN XY: 74324

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.263

Alfa AF: 0.244 Hom.: 561

Bravo AF: 0.253

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs7644007; hg19: chr3-3084279;