11-99819697-T-G

Variant names:

• chr11-99819697-T-G
• rs7125822
• NM_014361.4:c.209T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_014361.4(CNTN5):​c.209T>G​(p.Leu70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (0 hom., cov: 54)
  • Exomes 𝑓: 0.48 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNTN5 NM_014361.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.847
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017924607).
• BP6: Variant 11-99819697-T-G is Benign according to our data. Variant chr11-99819697-T-G is described in ClinVar as [Benign]. Clinvar id is 768471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN5	NM_014361.4	c.209T>G	p.Leu70Arg	missense_variant	Exon 4 of 25	ENST00000524871.6	NP_055176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN5	ENST00000524871.6	c.209T>G	p.Leu70Arg	missense_variant	Exon 4 of 25	1	NM_014361.4	ENSP00000435637.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 72605 AN: 149464 Hom.: 0 Cov.: 54

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.489

GnomAD2 exomes AF: 0.477 AC: 111638 AN: 233804 AF XY: 0.479

Gnomad AFR exome AF: 0.488

Gnomad AMR exome AF: 0.446

Gnomad ASJ exome AF: 0.496

Gnomad EAS exome AF: 0.393

Gnomad FIN exome AF: 0.485

Gnomad NFE exome AF: 0.495

Gnomad OTH exome AF: 0.486

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.485 AC: 643618 AN: 1328178 Hom.: 5 Cov.: 70 AF XY: 0.485 AC XY: 322173 AN XY: 664450

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.484 AC: 14566 AN: 30124

American (AMR) AF: 0.448 AC: 19005 AN: 42428

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 12419 AN: 25016

East Asian (EAS) AF: 0.388 AC: 14153 AN: 36478

South Asian (SAS) AF: 0.473 AC: 38016 AN: 80368

European-Finnish (FIN) AF: 0.484 AC: 24316 AN: 50204

Middle Eastern (MID) AF: 0.487 AC: 2629 AN: 5402

European-Non Finnish (NFE) AF: 0.490 AC: 491607 AN: 1002736

Other (OTH) AF: 0.485 AC: 26907 AN: 55422

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.486 AC: 72654 AN: 149574 Hom.: 0 Cov.: 54 AF XY: 0.484 AC XY: 35340 AN XY: 73004

African (AFR) AF: 0.488 AC: 19860 AN: 40698

American (AMR) AF: 0.466 AC: 6988 AN: 14996

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1703 AN: 3430

East Asian (EAS) AF: 0.406 AC: 2039 AN: 5016

South Asian (SAS) AF: 0.471 AC: 2192 AN: 4656

European-Finnish (FIN) AF: 0.485 AC: 5011 AN: 10338

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.495 AC: 33251 AN: 67164

Other (OTH) AF: 0.488 AC: 1015 AN: 2080

Alfa AF: 0.0930 Hom.: 13

ExAC AF: 0.475 AC: 57043

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 14, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.21
DEOGEN2	Benign	0.10	.;T;T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.20	T;.;T;T
MetaRNN	Benign	0.0018	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.8	N;N;N;.
PhyloP100		0.85
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.39	N;N;N;.
REVEL	Benign	0.12
Sift	Benign	1.0	T;T;T;.
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.20
MPC		0.045
ClinPred		0.0041	T
GERP RS		3.1
PromoterAI		0.033	Neutral
Varity_R		0.055
gMVP		0.31
Mutation Taster		=100/0	polymorphism

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: rs7125822; hg19: chr11-99690428; COSMIC: COSV54277807;