rs2406918

Variant names:

• chr11-99325420-G-T
• rs2406918
• NM_014361.4:c.-135G>T

Variant summary

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

The NM_014361.4(CNTN5):​c.-135G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,908 control chromosomes in the GnomAD database, including 7,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.31 (7569 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNTN5 NM_014361.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42
• Publications: 3 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=-0.48).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 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.-135G>T		5_prime_UTR	Exon 2 of 25	NP_055176.1	O94779-1
	CNTN5	NM_001243271.2		c.-135G>T		5_prime_UTR	Exon 2 of 21	NP_001230200.1	O94779-4
	CNTN5	NM_001243270.2		c.-70-230725G>T		intron	N/A	NP_001230199.1	O94779-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN5	ENST00000524871.6	TSL:1 MANE Select	c.-135G>T		5_prime_UTR	Exon 2 of 25	ENSP00000435637.1	O94779-1
	CNTN5	ENST00000527185.5	TSL:1	c.-135G>T		5_prime_UTR	Exon 2 of 21	ENSP00000433575.1	O94779-4
	CNTN5	ENST00000528727.5	TSL:1	n.370G>T		non_coding_transcript_exon	Exon 2 of 16

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47736 AN: 151794 Hom.: 7568 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.345

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.314 AC: 47753 AN: 151908 Hom.: 7569 Cov.: 32 AF XY: 0.306 AC XY: 22695 AN XY: 74214

African (AFR) AF: 0.304 AC: 12582 AN: 41446

American (AMR) AF: 0.259 AC: 3947 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1523 AN: 3468

East Asian (EAS) AF: 0.211 AC: 1087 AN: 5150

South Asian (SAS) AF: 0.333 AC: 1602 AN: 4814

European-Finnish (FIN) AF: 0.255 AC: 2686 AN: 10538

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23161 AN: 67926

Other (OTH) AF: 0.346 AC: 731 AN: 2112

Alfa AF: 0.325 Hom.: 3679

Bravo AF: 0.312

Asia WGS AF: 0.308 AC: 1071 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.65
PhyloP100		2.4
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2406918; hg19: chr11-99196151;