3-2571317-A-G

Variant names:

• chr3-2571317-A-G
• rs2616585
• NM_175607.3:c.-88-99A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_175607.3(CNTN4):​c.-88-99A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 625,356 control chromosomes in the GnomAD database, including 106,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24035 hom., cov: 33)
  • Exomes 𝑓: 0.58 (82780 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.111
• Publications: 5 publications found

Genes affected

CNTN4 (HGNC:2174): (contactin 4) This gene encodes a member of the contactin family of immunoglobulins. Contactins are axon-associated cell adhesion molecules that function in neuronal network formation and plasticity. The encoded protein is a glycosylphosphatidylinositol-anchored neuronal membrane protein that may play a role in the formation of axon connections in the developing nervous system. Deletion or mutation of this gene may play a role in 3p deletion syndrome and autism spectrum disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

CNTN4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• autism spectrum disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-2571317-A-G is Benign according to our data. Variant chr3-2571317-A-G is described in ClinVar as [Benign]. Clinvar id is 1286817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3	c.-88-99A>G		intron_variant	Intron 3 of 24	ENST00000418658.6	NP_783200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6	c.-88-99A>G		intron_variant	Intron 3 of 24	5	NM_175607.3	ENSP00000396010.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84338 AN: 151922 Hom.: 24028 Cov.: 33

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.565

GnomAD4 exome AF: 0.581 AC: 275077 AN: 473316 Hom.: 82780 Cov.: 4 AF XY: 0.585 AC XY: 146934 AN XY: 251246

African (AFR) AF: 0.487 AC: 6291 AN: 12922

American (AMR) AF: 0.739 AC: 16208 AN: 21934

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 8128 AN: 14802

East Asian (EAS) AF: 0.873 AC: 27090 AN: 31046

South Asian (SAS) AF: 0.669 AC: 31398 AN: 46952

European-Finnish (FIN) AF: 0.549 AC: 20379 AN: 37106

Middle Eastern (MID) AF: 0.560 AC: 1716 AN: 3062

European-Non Finnish (NFE) AF: 0.533 AC: 148462 AN: 278676

Other (OTH) AF: 0.574 AC: 15405 AN: 26816

GnomAD4 genome AF: 0.555 AC: 84378 AN: 152040 Hom.: 24035 Cov.: 33 AF XY: 0.562 AC XY: 41747 AN XY: 74322

African (AFR) AF: 0.498 AC: 20660 AN: 41470

American (AMR) AF: 0.679 AC: 10371 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1870 AN: 3470

East Asian (EAS) AF: 0.879 AC: 4533 AN: 5158

South Asian (SAS) AF: 0.674 AC: 3245 AN: 4818

European-Finnish (FIN) AF: 0.538 AC: 5674 AN: 10552

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36210 AN: 67972

Other (OTH) AF: 0.568 AC: 1199 AN: 2112

Alfa AF: 0.550 Hom.: 74700

Bravo AF: 0.563

Asia WGS AF: 0.771 AC: 2681 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.5
DANN	Benign	0.85
PhyloP100		0.11
PromoterAI		-0.022	Neutral
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: rs2616585; hg19: chr3-2613001;