11-99819775-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014361.4(CNTN5):c.277+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0041 (0 hom.)
• Consequence: CNTN5 NM_014361.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.495

Genes affected

CNTN5 (HGNC:2175): (contactin 5) The protein encoded by this gene is a member of the immunoglobulin superfamily, and contactin family, which mediate cell surface interactions during nervous system development. This protein is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-99819775-A-G is Benign according to our data. Variant chr11-99819775-A-G is described in ClinVar as [Benign]. Clinvar id is 3054065.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN5	NM_014361.4	c.277+10A>G		intron_variant		ENST00000524871.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN5	ENST00000524871.6	c.277+10A>G		intron_variant		1	NM_014361.4	P1

Frequencies

GnomAD3 genomes AF: 0.00707 AC: 67 AN: 9480 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00382

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0420

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0118 AC: 133 AN: 11318 Hom.: 1 AF XY: 0.0115 AC XY: 65 AN XY: 5630

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.00206

Gnomad SAS exome AF: 0.00484

Gnomad FIN exome AF: 0.0471

Gnomad NFE exome AF: 0.00895

Gnomad OTH exome AF: 0.00472

GnomAD4 exome AF: 0.00408 AC: 457 AN: 112034 Hom.: 0 Cov.: 4 AF XY: 0.00426 AC XY: 234 AN XY: 54982

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.00141

Gnomad4 SAS exome AF: 0.00361

Gnomad4 FIN exome AF: 0.0419

Gnomad4 NFE exome AF: 0.00104

Gnomad4 OTH exome AF: 0.00676

GnomAD4 genome AF: 0.00704 AC: 67 AN: 9520 Hom.: 0 Cov.: 0 AF XY: 0.00915 AC XY: 46 AN XY: 5028

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.00382

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0420

Gnomad4 NFE AF: 0.00245

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000898 Hom.: 0

Bravo AF: 0.000234

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CNTN5-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 21, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	13
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs201079661; hg19: chr11-99690506;