rs7125822

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-99819697-T-A
• chr11-99819697-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014361.4(CNTN5):​c.209T>A​(p.Leu70Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,594,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L70R) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 54)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: CNTN5 NM_014361.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.083253235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN5	NM_014361.4	c.209T>A	p.Leu70Gln	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>A	p.Leu70Gln	missense_variant	Exon 4 of 25	1	NM_014361.4	ENSP00000435637.1

Frequencies

GnomAD3 genomes AF: 0.0000396 AC: 6 AN: 151522 Hom.: 0 Cov.: 54

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000128 AC: 3 AN: 233804 AF XY: 0.00000781

Gnomad AFR exome AF: 0.000208

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000132 AC: 19 AN: 1442758 Hom.: 0 Cov.: 70 AF XY: 0.0000111 AC XY: 8 AN XY: 718162

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

African (AFR) AF: 0.000273 AC: 9 AN: 32952

American (AMR) AF: 0.00 AC: 0 AN: 44374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25964

East Asian (EAS) AF: 0.00 AC: 0 AN: 39410

South Asian (SAS) AF: 0.00 AC: 0 AN: 85172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000729 AC: 8 AN: 1097562

Other (OTH) AF: 0.0000335 AC: 2 AN: 59700

⚠️ 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 AF: 0.0000396 AC: 6 AN: 151522 Hom.: 0 Cov.: 54 AF XY: 0.0000406 AC XY: 3 AN XY: 73982

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

African (AFR) AF: 0.000121 AC: 5 AN: 41252

American (AMR) AF: 0.00 AC: 0 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67780

Other (OTH) AF: 0.00 AC: 0 AN: 2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.001080), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 13

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.099	.;T;T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.38	T;.;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.083	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N;.
PhyloP100		0.85
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.52	N;N;N;.
REVEL	Benign	0.16
Sift	Benign	0.13	T;T;T;.
Sift4G	Benign	0.29	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.26
MutPred		0.28		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);.;
MVP		0.41
MPC		0.036
ClinPred		0.025	T
GERP RS		3.1
PromoterAI		0.019	Neutral
Varity_R		0.058
gMVP		0.25
Mutation Taster		=96/4	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;