rs186615197

chr11-100061278-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014361.4(CNTN5):c.1047A>T(p.Lys349Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,613,660 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (14 hom.)
• Consequence: CNTN5 NM_014361.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.661

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]

LOC105369456 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009718627).
• BP6: Variant 11-100061278-A-T is Benign according to our data. Variant chr11-100061278-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 446039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00104 (1523/1461362) while in subpopulation AMR AF= 0.0178 (798/44716). AF 95% confidence interval is 0.0168. There are 14 homozygotes in gnomad4_exome. There are 698 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN5	NM_014361.4	c.1047A>T	p.Lys349Asn	missense_variant	10/25	ENST00000524871.6
LOC105369456	XR_947948.3	n.208-5748T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN5	ENST00000524871.6	c.1047A>T	p.Lys349Asn	missense_variant	10/25	1	NM_014361.4	P1

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 229 AN: 152180 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00950

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00393 AC: 978 AN: 248988 Hom.: 14 AF XY: 0.00319 AC XY: 431 AN XY: 135056

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.0191

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.0150

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00232

GnomAD4 exome AF: 0.00104 AC: 1523 AN: 1461362 Hom.: 14 Cov.: 31 AF XY: 0.000960 AC XY: 698 AN XY: 726968

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.0178

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.0120

Gnomad4 SAS exome AF: 0.000661

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000603

Gnomad4 OTH exome AF: 0.00177

GnomAD4 genome AF: 0.00150 AC: 229 AN: 152298 Hom.: 3 Cov.: 33 AF XY: 0.00153 AC XY: 114 AN XY: 74476

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00942

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0130

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000781 Hom.: 0

Bravo AF: 0.00264

ESP6500AA AF: 0.000260 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00306 AC: 370

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	22
Dann	Uncertain	1.0
Eigen	Benign	0.10
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.84	T;.;T;T;T;T
MetaRNN	Benign	0.0097	T;T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	-0.20	N;N;N;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.5	N;N;N;N;.;.
REVEL	Uncertain	0.46
Sift	Benign	0.11	T;T;T;T;.;.
Sift4G	Benign	0.15	T;T;T;T;T;T
Polyphen		1.0	.;D;D;D;.;.
Vest4		0.70
MutPred		0.59		Loss of MoRF binding (P = 0.0531);Loss of MoRF binding (P = 0.0531);Loss of MoRF binding (P = 0.0531);.;.;.;
MVP		0.77
MPC		0.28
ClinPred		0.042	T
GERP RS		1.9
Varity_R		0.19
gMVP		0.58

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: rs186615197; hg19: chr11-99932010;