3-3042756-T-G

Position:

• chr3-3042756-T-G

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.2512-221T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 602,142 control chromosomes in the GnomAD database, including 60,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (19604 hom., cov: 32)
  • Exomes 𝑓: 0.41 (40410 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.128

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=-0.81).
• BP6: Variant 3-3042756-T-G is Benign according to our data. Variant chr3-3042756-T-G is described in ClinVar as [Benign]. Clinvar id is 1281257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.2512-221T>G		intron_variant		ENST00000418658.6	NP_783200.1
CNTN4-AS1	NR_046554.1	n.180+157A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.2512-221T>G		intron_variant		5	NM_175607.3	ENSP00000396010	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74270 AN: 151812 Hom.: 19561 Cov.: 32

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.411 AC: 185132 AN: 450210 Hom.: 40410 AF XY: 0.405 AC XY: 96825 AN XY: 239316

Gnomad4 AFR exome AF: 0.684

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.440

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.490 AC: 74371 AN: 151932 Hom.: 19604 Cov.: 32 AF XY: 0.482 AC XY: 35824 AN XY: 74274

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.491

Alfa AF: 0.478 Hom.: 2218

Bravo AF: 0.503

Asia WGS AF: 0.242 AC: 839 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	-0.81
CADD	Benign	4.9
DANN	Benign	0.38

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: rs467919; hg19: chr3-3084440;