11-99917321-A-G

Variant names:

• chr11-99917321-A-G
• rs10501934
• NM_014361.4:c.673+1172A>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.673+1172A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 152,180 control chromosomes in the GnomAD database, including 257 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 0.040 (257 hom., cov: 32)
• Consequence: CNTN5 NM_014361.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694
• Publications: 0 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.098 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN5	NM_014361.4	MANE Select	c.673+1172A>G		intron	N/A	NP_055176.1
	CNTN5	NM_001243270.2		c.673+1172A>G		intron	N/A	NP_001230199.1
	CNTN5	NM_175566.2		c.451+1172A>G		intron	N/A	NP_780775.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN5	ENST00000524871.6	TSL:1 MANE Select	c.673+1172A>G		intron	N/A	ENSP00000435637.1
	CNTN5	ENST00000418526.6	TSL:1	c.451+1172A>G		intron	N/A	ENSP00000393229.2
	CNTN5	ENST00000527185.5	TSL:1	c.673+1172A>G		intron	N/A	ENSP00000433575.1

Frequencies

GnomAD3 genomes AF: 0.0399 AC: 6072 AN: 152062 Hom.: 253 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0578

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0526

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.00640

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00643

Gnomad OTH AF: 0.0339

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

GnomAD4 genome AF: 0.0401 AC: 6101 AN: 152180 Hom.: 257 Cov.: 32 AF XY: 0.0406 AC XY: 3022 AN XY: 74402

African (AFR) AF: 0.100 AC: 4171 AN: 41504

American (AMR) AF: 0.0584 AC: 892 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.0528 AC: 273 AN: 5174

South Asian (SAS) AF: 0.0324 AC: 156 AN: 4822

European-Finnish (FIN) AF: 0.00640 AC: 68 AN: 10622

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.00644 AC: 438 AN: 68000

Other (OTH) AF: 0.0345 AC: 73 AN: 2114

Alfa AF: 0.0241 Hom.: 32

Bravo AF: 0.0472

Asia WGS AF: 0.0660 AC: 227 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.33
DANN	Benign	0.65
PhyloP100		-0.69
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: rs10501934; hg19: chr11-99788053;