11-99117578-A-G

Variant names:

• chr11-99117578-A-G
• rs4753939
• NM_014361.4:c.-210+96308A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014361.4(CNTN5):​c.-210+96308A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,020 control chromosomes in the GnomAD database, including 22,782 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22782 hom., cov: 32)
• Consequence: CNTN5 NM_014361.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 7 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 (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014361.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN5	NM_014361.4	MANE Select	c.-210+96308A>G		intron	N/A	NP_055176.1	O94779-1
	CNTN5	NM_001243270.2		c.-71+96308A>G		intron	N/A	NP_001230199.1	O94779-1
	CNTN5	NM_001243271.2		c.-210+96308A>G		intron	N/A	NP_001230200.1	O94779-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN5	ENST00000524871.6	TSL:1 MANE Select	c.-210+96308A>G		intron	N/A	ENSP00000435637.1	O94779-1
	CNTN5	ENST00000527185.5	TSL:1	c.-210+96308A>G		intron	N/A	ENSP00000433575.1	O94779-4
	CNTN5	ENST00000528727.5	TSL:1	n.295+96308A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82474 AN: 151902 Hom.: 22765 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.543 AC: 82528 AN: 152020 Hom.: 22782 Cov.: 32 AF XY: 0.548 AC XY: 40691 AN XY: 74284

African (AFR) AF: 0.413 AC: 17115 AN: 41452

American (AMR) AF: 0.642 AC: 9799 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1598 AN: 3468

East Asian (EAS) AF: 0.614 AC: 3173 AN: 5170

South Asian (SAS) AF: 0.543 AC: 2612 AN: 4812

European-Finnish (FIN) AF: 0.631 AC: 6667 AN: 10562

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39670 AN: 67974

Other (OTH) AF: 0.557 AC: 1175 AN: 2108

Alfa AF: 0.570 Hom.: 40083

Bravo AF: 0.542

Asia WGS AF: 0.591 AC: 2053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.94
DANN	Benign	0.54
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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: rs4753939; hg19: chr11-98988308;